WorldWideScience

Sample records for tissue construct mechanics

  1. Bioprinting of hybrid tissue constructs with tailorable mechanical properties

    Energy Technology Data Exchange (ETDEWEB)

    Schuurman, W; Khristov, V; Pot, M W; Dhert, W J A; Malda, J [Department of Orthopaedics, University Medical Center Utrecht (Netherlands); Van Weeren, P R, E-mail: j.malda@umcutrecht.nl [Faculty of Veterinary Sciences, Department of Equine Sciences, Utrecht University (Netherlands)

    2011-06-15

    Tissue/organ printing aims to recapitulate the intrinsic complexity of native tissues. For a number of tissues, in particular those of musculoskeletal origin, adequate mechanical characteristics are an important prerequisite for their initial handling and stability, as well as long-lasting functioning. Hence, organized implants, possessing mechanical characteristics similar to the native tissue, may result in improved clinical outcomes of regenerative approaches. Using a bioprinter, grafts were constructed by alternate deposition of thermoplastic fibers and (cell-laden) hydrogels. Constructs of different shapes and sizes were manufactured and mechanical properties, as well as cell viability, were assessed. This approach yields novel organized viable hybrid constructs, which possess favorable mechanical characteristics, within the same range as those of native tissues. Moreover, the approach allows the use of multiple hydrogels and can thus produce constructs containing multiple cell types or bioactive factors. Furthermore, since the hydrogel is supported by the thermoplastic material, a broader range of hydrogel types can be used compared to bioprinting of hydrogels alone. In conclusion, we present an innovative and versatile approach for bioprinting, yielding constructs of which the mechanical stiffness provided by thermoplastic polymers can potentially be tailored, and combined specific cell placement patterns of multiple cell types embedded in a wide range of hydrogels. (communication)

  2. Electrical and mechanical stimulation of cardiac cells and tissue constructs.

    Science.gov (United States)

    Stoppel, Whitney L; Kaplan, David L; Black, Lauren D

    2016-01-15

    The field of cardiac tissue engineering has made significant strides over the last few decades, highlighted by the development of human cell derived constructs that have shown increasing functional maturity over time, particularly using bioreactor systems to stimulate the constructs. However, the functionality of these tissues is still unable to match that of native cardiac tissue and many of the stem-cell derived cardiomyocytes display an immature, fetal like phenotype. In this review, we seek to elucidate the biological underpinnings of both mechanical and electrical signaling, as identified via studies related to cardiac development and those related to an evaluation of cardiac disease progression. Next, we review the different types of bioreactors developed to individually deliver electrical and mechanical stimulation to cardiomyocytes in vitro in both two and three-dimensional tissue platforms. Reactors and culture conditions that promote functional cardiomyogenesis in vitro are also highlighted. We then cover the more recent work in the development of bioreactors that combine electrical and mechanical stimulation in order to mimic the complex signaling environment present in vivo. We conclude by offering our impressions on the important next steps for physiologically relevant mechanical and electrical stimulation of cardiac cells and engineered tissue in vitro. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Online monitoring of mechanical properties of three-dimensional tissue engineered constructs for quality assessment

    Science.gov (United States)

    Reinwald, Yvonne; Bagnaninchi, Pierre O.; Yang, Ying; Baba Ismail, Yanny M.; El Haj, Alicia J.

    2016-03-01

    Mechanical preconditioning and mechanical properties of tissue engineered constructs are essential for their capability to regenerate damaged tissues. To online monitor the mechanical properties a hydrostatic pressure bioreactor was coupled with optical coherence tomography into a new image modality termed hydrostatic pressure optical coherence elastography (HP-OCE). HP-OCE was utilised to assess the properties of three-dimensional (3D) tissue constructs while being physically stimulated within the hydrostatic force bioreactor. Hydrogels have been infiltrated into porous rapid prototyped or salt-leached scaffolds to mimic heterogeneous mechanical properties of cell-seeded constructs. Variations of mechanical properties in the solid scaffolds and agarose gels with different gel concentrations as well as the presences of cells have been clearly delineated by HP-OCE. Results indicate that HP-OCE allows contactless real-time non-invasive monitoring of the mechanical properties of tissue constructs and the effect of physical stimulation on cellular activities.

  4. Design and Validation of Equiaxial Mechanical Strain Platform, EQUicycler, for 3D Tissue Engineered Constructs.

    Science.gov (United States)

    Elsaadany, Mostafa; Harris, Matthew; Yildirim-Ayan, Eda

    2017-01-01

    It is crucial to replicate the micromechanical milieu of native tissues to achieve efficacious tissue engineering and regenerative therapy. In this study, we introduced an innovative loading platform, EQUicycler, that utilizes a simple, yet effective, and well-controlled mechanism to apply physiologically relevant homogenous mechanical equiaxial strain on three-dimensional cell-embedded tissue scaffolds. The design of EQUicycler ensured elimination of gripping effects through the use of biologically compatible silicone posts for direct transfer of the mechanical load to the scaffolds. Finite Element Modeling (FEM) was created to understand and to quantify how much applied global strain was transferred from the loading mechanism to the tissue constructs. In vitro studies were conducted on various cell lines associated with tissues exposed to equiaxial mechanical loading in their native environment. In vitro results demonstrated that EQUicycler was effective in maintaining and promoting the viability of different musculoskeletal cell lines and upregulating early differentiation of osteoprogenitor cells. By utilizing EQUicycler, collagen fibers of the constructs were actively remodeled. Residing cells within the collagen construct elongated and aligned with strain direction upon mechanical loading. EQUicycler can provide an efficient and cost-effective tool to conduct mechanistic studies for tissue engineered constructs designed for tissue systems under mechanical loading in vivo.

  5. Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications

    International Nuclear Information System (INIS)

    Xu Tao; Binder, Kyle W; Albanna, Mohammad Z; Dice, Dennis; Zhao Weixin; Yoo, James J; Atala, Anthony

    2013-01-01

    Bioprinting is an emerging technique used to fabricate viable, 3D tissue constructs through the precise deposition of cells and hydrogels in a layer-by-layer fashion. Despite the ability to mimic the native properties of tissue, printed 3D constructs that are composed of naturally-derived biomaterials still lack structural integrity and adequate mechanical properties for use in vivo, thus limiting their development for use in load-bearing tissue engineering applications, such as cartilage. Fabrication of viable constructs using a novel multi-head deposition system provides the ability to combine synthetic polymers, which have higher mechanical strength than natural materials, with the favorable environment for cell growth provided by traditional naturally-derived hydrogels. However, the complexity and high cost associated with constructing the required robotic system hamper the widespread application of this approach. Moreover, the scaffolds fabricated by these robotic systems often lack flexibility, which further restrict their applications. To address these limitations, advanced fabrication techniques are necessary to generate complex constructs with controlled architectures and adequate mechanical properties. In this study, we describe the construction of a hybrid inkjet printing/electrospinning system that can be used to fabricate viable tissues for cartilage tissue engineering applications. Electrospinning of polycaprolactone fibers was alternated with inkjet printing of rabbit elastic chondrocytes suspended in a fibrin–collagen hydrogel in order to fabricate a five-layer tissue construct of 1 mm thickness. The chondrocytes survived within the printed hybrid construct with more than 80% viability one week after printing. In addition, the cells proliferated and maintained their basic biological properties within the printed layered constructs. Furthermore, the fabricated constructs formed cartilage-like tissues both in vitro and in vivo as evidenced by the

  6. A Novel Pulsatile Bioreactor for Mechanical Stimulation of Tissue Engineered Cardiac Constructs

    Directory of Open Access Journals (Sweden)

    Günther Eissner

    2011-07-01

    Full Text Available After myocardial infarction, the implantation of stem cell seeded scaffolds on the ischemic zone represents a promising strategy for restoration of heart function. However, mechanical integrity and functionality of tissue engineered constructs need to be determined prior to implantation. Therefore, in this study a novel pulsatile bioreactor mimicking the myocardial contraction was developed to analyze the behavior of mesenchymal stem cells derived from umbilical cord tissue (UCMSC colonized on titanium-coated polytetrafluorethylene scaffolds to friction stress. The design of the bioreactor enables a simple handling and defined mechanical forces on three seeded scaffolds at physiological conditions. The compact system made of acrylic glass, Teflon®, silicone, and stainless steel allows the comparison of different media, cells and scaffolds. The bioreactor can be gas sterilized and actuated in a standard incubator. Macroscopic observations and pressure-measurements showed a uniformly sinusoidal pulsation, indicating that the bioreactor performed well. Preliminary experiments to determine the adherence rate and morphology of UCMSC after mechanical loadings showed an almost confluent cellular coating without damage on the cell surface. In summary, the bioreactor is an adequate tool for the mechanical stress of seeded scaffolds and offers dynamic stimuli for pre-conditioning of cardiac tissue engineered constructs in vitro.

  7. Engineering tissue constructs to mimic native aortic and pulmonary valve leaflets' structures and mechanics

    Science.gov (United States)

    Masoumi, Nafiseh

    There are several disadvantages correlated with current heart valve replacement, including anticoagulation therapy for patients with mechanical valves and the low durability of bioprosthetic valves. The non-viable nature of such devices is a critical drawback especially for pediatric cases due to the inability of the graft to grow in vivo with the patients. A tissue engineered heart valve (TEHV) with remodeling and growth ability, is conceptually appealing to use in the surgical repair and could serve as a permanent replacements when operating for pediatric valvular lesions. It is critical that scaffolds for functional heart valve tissue engineering, be capable of mimicking the native leaflet's structure and mechanical properties at the time of implantation. Meanwhile, the scaffolds should be able to support cellular proliferation and native-like tissue formation as the TEHV remodels toward a scaffold-free state. Our overall hypothesis is that an "ideal" engineered construct, designed based on native leaflet's structure and mechanics, will complement a native heart valve leaflet in providing benchmarks for use in the design of clinically-applicable TEHV. This hypothesis was addressed through several experiments conducted in the present study. To establish a functional biomimetic TEHV, we developed scaffolds capable of matching the anisotropic stiffness of native leaflet while promoting native-like cell and collagen content and supporting the ECM generation. Scaffolds with various polymer contents (e.g., poly (glycerol sebacate) (PGS) and poly (epsilon-caprolactone) (PCL)) and structural designs (e.g., microfabricated and microfibrous scaffolds), were fabricated based on native leaflet's structure and mechanics. It was found that the tri-layered scaffold, designed with assembly of microfabricated PGS and microfibrous PGS/PCL was a functional leaflet capable of promoting tissue formation. Furthermore, to investigate the effect of cyclic stress and flexure

  8. Mechanical stretching for tissue engineering: two-dimensional and three-dimensional constructs.

    Science.gov (United States)

    Riehl, Brandon D; Park, Jae-Hong; Kwon, Il Keun; Lim, Jung Yul

    2012-08-01

    Mechanical cell stretching may be an attractive strategy for the tissue engineering of mechanically functional tissues. It has been demonstrated that cell growth and differentiation can be guided by cell stretch with minimal help from soluble factors and engineered tissues that are mechanically stretched in bioreactors may have superior organization, functionality, and strength compared with unstretched counterparts. This review explores recent studies on cell stretching in both two-dimensional (2D) and three-dimensional (3D) setups focusing on the applications of stretch stimulation as a tool for controlling cell orientation, growth, gene expression, lineage commitment, and differentiation and for achieving successful tissue engineering of mechanically functional tissues, including cardiac, muscle, vasculature, ligament, tendon, bone, and so on. Custom stretching devices and lab-specific mechanical bioreactors are described with a discussion on capabilities and limitations. While stretch mechanotransduction pathways have been examined using 2D stretch, studying such pathways in physiologically relevant 3D environments may be required to understand how cells direct tissue development under stretch. Cell stretch study using 3D milieus may also help to develop tissue-specific stretch regimens optimized with biochemical feedback, which once developed will provide optimal tissue engineering protocols.

  9. Supplementation of exogenous adenosine 5'-triphosphate enhances mechanical properties of 3D cell-agarose constructs for cartilage tissue engineering.

    Science.gov (United States)

    Gadjanski, Ivana; Yodmuang, Supansa; Spiller, Kara; Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana

    2013-10-01

    Formation of tissue-engineered cartilage is greatly enhanced by mechanical stimulation. However, direct mechanical stimulation is not always a suitable method, and the utilization of mechanisms underlying mechanotransduction might allow for a highly effective and less aggressive alternate means of stimulation. In particular, the purinergic, adenosine 5'-triphosphate (ATP)-mediated signaling pathway is strongly implicated in mechanotransduction within the articular cartilage. We investigated the effects of transient and continuous exogenous ATP supplementation on mechanical properties of cartilaginous constructs engineered using bovine chondrocytes and human mesenchymal stem cells (hMSCs) encapsulated in an agarose hydrogel. For both cell types, we have observed significant increases in equilibrium and dynamic compressive moduli after transient ATP treatment applied in the fourth week of cultivation. Continuous ATP treatment over 4 weeks of culture only slightly improved the mechanical properties of the constructs, without major changes in the total glycosaminoglycan (GAG) and collagen content. Structure-function analyses showed that transiently ATP-treated constructs, and in particular those based on hMSCs, had the highest level of correlation between compositional and mechanical properties. Transiently treated groups showed intense staining of the territorial matrix for GAGs and collagen type II. These results indicate that transient ATP treatment can improve functional mechanical properties of cartilaginous constructs based on chondrogenic cells and agarose hydrogels, possibly by improving the structural organization of the bulk phase and territorial extracellular matrix (ECM), that is, by increasing correlation slopes between the content of the ECM components (GAG, collagen) and mechanical properties of the construct.

  10. Bioprinting of a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system

    International Nuclear Information System (INIS)

    Shim, Jin-Hyung; Lee, Jung-Seob; Cho, Dong-Woo; Kim, Jong Young

    2012-01-01

    The aim of this study was to build a mechanically enhanced three-dimensional (3D) bioprinted construct containing two different cell types for osteochondral tissue regeneration. Recently, the production of 3D cell-laden structures using various scaffold-free cell printing technologies has opened up new possibilities. However, ideal 3D complex tissues or organs have not yet been printed because gel-state hydrogels have been used as the principal material and are unable to maintain the desired 3D structure due to their poor mechanical strength. In this study, thermoplastic biomaterial polycaprolactone (PCL), which shows relatively high mechanical properties as compared with hydrogel, was used as a framework for enhancing the mechanical stability of the bioprinted construct. Two different alginate solutions were then infused into the previously prepared framework consisting of PCL to create the 3D construct for osteochondral printing. For this work, a multi-head tissue/organ building system (MtoBS), which was particularly designed to dispense thermoplastic biomaterial and hydrogel having completely different rheology properties, was newly developed and used to bioprint osteochondral tissue. It was confirmed that the line width, position and volume control of PCL and alginate solutions were adjustable in the MtoBS. Most importantly, dual cell-laden 3D constructs consisting of osteoblasts and chondrocytes were successfully fabricated. Further, the separately dispensed osteoblasts and chondrocytes not only retained their initial position and viability, but also proliferated up to 7 days after being dispensed. (paper)

  11. Compressed collagen constructs with optimized mechanical properties and cell interactions for tissue engineering applications

    DEFF Research Database (Denmark)

    Ajalloueian, Fatemeh; Nikogeorgos, Nikolaos; Ajalloueian, Ali

    2018-01-01

    In this study, we are introducing a simple, fast and reliable add-in to the technique of plastic compression (PC) to obtain collagen sheets with decreased fibrillar densities, representing improved cell-interactions and mechanical properties. Collagen hydrogels with different initial concentrations...... for plastic compression, not only a better cell environment and optimum mechanical properties are achieved, but also the application costs of this biopolymer is reduced....

  12. Design, construction and mechanical testing of digital 3D anatomical data-based PCL-HA bone tissue engineering scaffold.

    Science.gov (United States)

    Yao, Qingqiang; Wei, Bo; Guo, Yang; Jin, Chengzhe; Du, Xiaotao; Yan, Chao; Yan, Junwei; Hu, Wenhao; Xu, Yan; Zhou, Zhi; Wang, Yijin; Wang, Liming

    2015-01-01

    The study aims to investigate the techniques of design and construction of CT 3D reconstructional data-based polycaprolactone (PCL)-hydroxyapatite (HA) scaffold. Femoral and lumbar spinal specimens of eight male New Zealand white rabbits were performed CT and laser scanning data-based 3D printing scaffold processing using PCL-HA powder. Each group was performed eight scaffolds. The CAD-based 3D printed porous cylindrical stents were 16 piece × 3 groups, including the orthogonal scaffold, the Pozi-hole scaffold and the triangular hole scaffold. The gross forms, fiber scaffold diameters and porosities of the scaffolds were measured, and the mechanical testing was performed towards eight pieces of the three kinds of cylindrical scaffolds, respectively. The loading force, deformation, maximum-affordable pressure and deformation value were recorded. The pore-connection rate of each scaffold was 100 % within each group, there was no significant difference in the gross parameters and micro-structural parameters of each scaffold when compared with the design values (P > 0.05). There was no significant difference in the loading force, deformation and deformation value under the maximum-affordable pressure of the three different cylinder scaffolds when the load was above 320 N. The combination of CT and CAD reverse technology could accomplish the design and manufacturing of complex bone tissue engineering scaffolds, with no significant difference in the impacts of the microstructures towards the physical properties of different porous scaffolds under large load.

  13. In vitro culture increases mechanical stability of human tissue engineered cartilage constructs by prevention of microscale scaffold buckling.

    Science.gov (United States)

    Middendorf, Jill M; Shortkroff, Sonya; Dugopolski, Caroline; Kennedy, Stephen; Siemiatkoski, Joseph; Bartell, Lena R; Cohen, Itai; Bonassar, Lawrence J

    2017-11-07

    Many studies have measured the global compressive properties of tissue engineered (TE) cartilage grown on porous scaffolds. Such scaffolds are known to exhibit strain softening due to local buckling under loading. As matrix is deposited onto these scaffolds, the global compressive properties increase. However the relationship between the amount and distribution of matrix in the scaffold and local buckling is unknown. To address this knowledge gap, we studied how local strain and construct buckling in human TE constructs changes over culture times and GAG content. Confocal elastography techniques and digital image correlation (DIC) were used to measure and record buckling modes and local strains. Receiver operating characteristic (ROC) curves were used to quantify construct buckling. The results from the ROC analysis were placed into Kaplan-Meier survival function curves to establish the probability that any point in a construct buckled. These analysis techniques revealed the presence of buckling at early time points, but bending at later time points. An inverse correlation was observed between the probability of buckling and the total GAG content of each construct. This data suggests that increased GAG content prevents the onset of construct buckling and improves the microscale compressive tissue properties. This increase in GAG deposition leads to enhanced global compressive properties by prevention of microscale buckling. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Vascularization of soft tissue engineering constructs

    DEFF Research Database (Denmark)

    Pimentel Carletto, Rodrigo

    with mechanical properties in the range of soft tissues has not been fully achieved. My project focused on the fabrication and the active perfusion of hydrogel constructs with multi-dimensional vasculature and controlled mechanical properties targeting soft tissues. Specifically, the initial part of the research...... nanotechnology-based paradigm for engineering vascularised liver tissue for transplantation”) and the Danish National Research Foundation and Villum Foundation’s Center for Intelligent Drug delivery and sensing Using microcontainers and Nanomechanics (Danish National Research Foundation (DNRF122)....

  15. The effect of mechanical stimulation on the maturation of TDSCs-poly(L-lactide-co-e-caprolactone)/collagen scaffold constructs for tendon tissue engineering.

    Science.gov (United States)

    Xu, Yuan; Dong, Shiwu; Zhou, Qiang; Mo, Xiumei; Song, Lei; Hou, Tianyong; Wu, Jinglei; Li, Songtao; Li, Yudong; Li, Pei; Gan, Yibo; Xu, Jianzhong

    2014-03-01

    Mechanical stimulation plays an important role in the development and remodeling of tendons. Tendon-derived stem cells (TDSCs) are an attractive cell source for tendon injury and tendon tissue engineering. However, these cells have not yet been fully explored for tendon tissue engineering application, and there is also lack of understanding to the effect of mechanical stimulation on the maturation of TDSCs-scaffold construct for tendon tissue engineering. In this study, we assessed the efficacy of TDSCs in a poly(L-lactide-co-ε-caprolactone)/collagen (P(LLA-CL)/Col) scaffold under mechanical stimulation for tendon tissue engineering both in vitro and in vivo, and evaluated the utility of the transplanted TDSCs-scaffold construct to promote rabbit patellar tendon defect regeneration. TDSCs displayed good proliferation and positive expressed tendon-related extracellular matrix (ECM) genes and proteins under mechanical stimulation in vitro. After implanting into the nude mice, the fluorescence imaging indicated that TDSCs had long-term survival, and the macroscopic evaluation, histology and immunohistochemistry examinations showed high-quality neo-tendon formation under mechanical stimulation in vivo. Furthermore, the histology, immunohistochemistry, collagen content assay and biomechanical testing data indicated that dynamically cultured TDSCs-scaffold construct could significantly contributed to tendon regeneration in a rabbit patellar tendon window defect model. TDSCs have significant potential to be used as seeded cells in the development of tissue-engineered tendons, which can be successfully fabricated through seeding of TDSCs in a P(LLA-CL)/Col scaffold followed by mechanical stimulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. In vitro generation of a scaffold-free tissue-engineered construct (TEC) derived from human synovial mesenchymal stem cells: biological and mechanical properties and further chondrogenic potential.

    Science.gov (United States)

    Ando, Wataru; Tateishi, Kosuke; Katakai, Daisuke; Hart, David A; Higuchi, Chikahisa; Nakata, Ken; Hashimoto, Jun; Fujie, Hiromichi; Shino, Konsei; Yoshikawa, Hideki; Nakamura, Norimasa

    2008-12-01

    The purpose of this study was to characterize a tissue-engineered construct (TEC) generated with human synovial mesenchymal stem cells (MSCs). MSCs were cultured in medium with ascorbic acid 2-phosphate (Asc-2P) and were subsequently detached from the substratum. The detached cell/matrix complex spontaneously contracted to develop a basic TEC. The volume of the TEC assessed by varying initial cell density showed that it was proportional to initial cell densities up to 4 x 10(5) cells/cm(2). Assessment of the mechanical properties of TEC using a custom device showed that the load at failure and stiffness of the constructs significantly increased with time of culture in the presence of Asc-2P, while in the absence of Asc-2P, the constructs were mechanically weak. Thus, the basic TEC possesses sufficiently self-supporting mechanical properties in spite of not containing artificial scaffolding. TEC further cultured in chondrogenic media exhibited positive alcian blue staining with elevated expression of chondrogenic marker genes. Based on these findings, such human TEC may be a promising method to promote cartilage repair for future clinical application.

  17. Variation in tissue outcome of ovine and human engineered heart valve constructs: relevance for tissue engineering.

    Science.gov (United States)

    van Geemen, Daphne; Driessen-Mol, Anita; Grootzwagers, Leonie G M; Soekhradj-Soechit, R Sarita; Riem Vis, Paul W; Baaijens, Frank P T; Bouten, Carlijn V C

    2012-01-01

    Clinical application of tissue engineered heart valves requires precise control of the tissue culture process to predict tissue composition and mechanical properties prior to implantation, and to understand the variation in tissue outcome. To this end we investigated cellular phenotype and tissue properties of ovine (n = 8) and human (n = 7) tissue engineered heart valve constructs to quantify variations in tissue outcome within species, study the differences between species and determine possible indicators of tissue outcome. Tissue constructs consisted of polyglycolic acid/poly-4-hydroxybutyrate scaffolds, seeded with myofibroblasts obtained from the jugular vein (sheep) or the saphenous vein (from humans undergoing cardiac surgery) and cultured under static conditions. Prior to seeding, protein expression of α-smooth muscle actin, vimentin, nonmuscle myosin heavy chain and heat shock protein 47 were determined to identify differences at an early stage of the tissue engineering process. After 4 weeks of culture, tissue composition and mechanical properties were quantified as indicators of tissue outcome. After 4 weeks of tissue culture, tissue properties of all ovine constructs were comparable, while there was a larger variation in the properties of the human constructs, especially the elastic modulus and collagen content. In addition, ovine constructs differed in composition from the human constructs. An increased number of α-smooth muscle actin-positive cells before seeding was correlated with the collagen content in the engineered heart valve constructs. Moreover, tissue stiffness increased with increasing collagen content. The results suggest that the culture process of ovine tissues can be controlled, whereas the mechanical properties, and hence functionality, of tissues originating from human material are more difficult to control. On-line evaluation of tissue properties during culture or more early cellular markers to predict the properties of autologous

  18. Cell Sheet-Based Tissue Engineering for Organizing Anisotropic Tissue Constructs Produced Using Microfabricated Thermoresponsive Substrates.

    Science.gov (United States)

    Takahashi, Hironobu; Okano, Teruo

    2015-11-18

    In some native tissues, appropriate microstructures, including orientation of the cell/extracellular matrix, provide specific mechanical and biological functions. For example, skeletal muscle is made of oriented myofibers that is responsible for the mechanical function. Native artery and myocardial tissues are organized three-dimensionally by stacking sheet-like tissues of aligned cells. Therefore, to construct any kind of complex tissue, the microstructures of cells such as myotubes, smooth muscle cells, and cardiomyocytes also need to be organized three-dimensionally just as in the native tissues of the body. Cell sheet-based tissue engineering allows the production of scaffold-free engineered tissues through a layer-by-layer construction technique. Recently, using microfabricated thermoresponsive substrates, aligned cells are being harvested as single continuous cell sheets. The cell sheets act as anisotropic tissue units to build three-dimensional tissue constructs with the appropriate anisotropy. This cell sheet-based technology is straightforward and has the potential to engineer a wide variety of complex tissues. In addition, due to the scaffold-free cell-dense environment, the physical and biological cell-cell interactions of these cell sheet constructs exhibit unique cell behaviors. These advantages will provide important clues to enable the production of well-organized tissues that closely mimic the structure and function of native tissues, required for the future of tissue engineering. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Mechanical device for tissue regeneration

    NARCIS (Netherlands)

    Herder, J.L.; Maij, E.

    2010-01-01

    The invention relates to a mechanical device for tissue- regeneration inside a patient, comprising means (2, 3) to place a scaffold for the tissue under mechanical stress. Said means comprise a first device-part (2) and a second device-part (3) which parts are arranged to be movable with respect to

  20. Multiscale mechanical modeling of soft biological tissues

    Science.gov (United States)

    Stylianopoulos, Triantafyllos

    2008-10-01

    Soft biological tissues include both native and artificial tissues. In the human body, tissues like the articular cartilage, arterial wall, and heart valve leaflets are examples of structures composed of an underlying network of collagen fibers, cells, proteins and molecules. Artificial tissues are less complex than native tissues and mainly consist of a fiber polymer network with the intent of replacing lost or damaged tissue. Understanding of the mechanical function of these materials is essential for many clinical treatments (e.g. arterial clamping, angioplasty), diseases (e.g. arteriosclerosis) and tissue engineering applications (e.g. engineered blood vessels or heart valves). This thesis presents the derivation and application of a multiscale methodology to describe the macroscopic mechanical function of soft biological tissues incorporating directly their structural architecture. The model, which is based on volume averaging theory, accounts for structural parameters such as the network volume fraction and orientation, the realignment of the fibers in response to strain, the interactions among the fibers and the interactions between the fibers and the interstitial fluid in order to predict the overall tissue behavior. Therefore, instead of using a constitutive equation to relate strain to stress, the tissue microstructure is modeled within a representative volume element (RVE) and the macroscopic response at any point in the tissue is determined by solving a micromechanics problem in the RVE. The model was applied successfully to acellular collagen gels, native blood vessels, and electrospun polyurethane scaffolds and provided accurate predictions for permeability calculations in isotropic and oriented fiber networks. The agreement of model predictions with experimentally determined mechanical properties provided insights into the mechanics of tissues and tissue constructs, while discrepancies revealed limitations of the model framework.

  1. Biomechanical properties of native and tissue engineered heart valve constructs.

    Science.gov (United States)

    Hasan, Anwarul; Ragaert, Kim; Swieszkowski, Wojciech; Selimović, Seila; Paul, Arghya; Camci-Unal, Gulden; Mofrad, Mohammad R K; Khademhosseini, Ali

    2014-06-27

    Due to the increasing number of heart valve diseases, there is an urgent clinical need for off-the-shelf tissue engineered heart valves. While significant progress has been made toward improving the design and performance of both mechanical and tissue engineered heart valves (TEHVs), a human implantable, functional, and viable TEHV has remained elusive. In animal studies so far, the implanted TEHVs have failed to survive more than a few months after transplantation due to insufficient mechanical properties. Therefore, the success of future heart valve tissue engineering approaches depends on the ability of the TEHV to mimic and maintain the functional and mechanical properties of the native heart valves. However, aside from some tensile quasistatic data and flexural or bending properties, detailed mechanical properties such as dynamic fatigue, creep behavior, and viscoelastic properties of heart valves are still poorly understood. The need for better understanding and more detailed characterization of mechanical properties of tissue engineered, as well as native heart valve constructs is thus evident. In the current review we aim to present an overview of the current understanding of the mechanical properties of human and common animal model heart valves. The relevant data on both native and tissue engineered heart valve constructs have been compiled and analyzed to help in defining the target ranges for mechanical properties of TEHV constructs, particularly for the aortic and the pulmonary valves. We conclude with a summary of perspectives on the future work on better understanding of the mechanical properties of TEHV constructs. © 2013 Published by Elsevier Ltd.

  2. The interplay between tissue growth and scaffold degradation in engineered tissue constructs

    KAUST Repository

    O’Dea, R. D.

    2012-09-18

    In vitro tissue engineering is emerging as a potential tool to meet the high demand for replacement tissue, caused by the increased incidence of tissue degeneration and damage. A key challenge in this field is ensuring that the mechanical properties of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation. In this paper, we use a mathematical model (based upon a multiphase continuum framework) to investigate the interplay between tissue growth and scaffold degradation during tissue construct evolution in vitro. Our model accommodates a cell population and culture medium, modelled as viscous fluids, together with a porous scaffold and ECM deposited by the cells, represented as rigid porous materials. We focus on tissue growth within a perfusion bioreactor system, and investigate how the predicted tissue composition is altered under the influence of (1) differential interactions between cells and the supporting scaffold and their associated ECM, (2) scaffold degradation, and (3) mechanotransduction-regulated cell proliferation and ECM deposition. Numerical simulation of the model equations reveals that scaffold heterogeneity typical of that obtained from μCT scans of tissue engineering scaffolds can lead to significant variation in the flow-induced mechanical stimuli experienced by cells seeded in the scaffold. This leads to strong heterogeneity in the deposition of ECM. Furthermore, preferential adherence of cells to the ECM in favour of the artificial scaffold appears to have no significant influence on the eventual construct composition; adherence of cells to these supporting structures does, however, lead to cell and ECM distributions which mimic and exaggerate the heterogeneity of the underlying scaffold. Such phenomena have important ramifications for the mechanical integrity of

  3. Automated 3D bioassembly of micro-tissues for biofabrication of hybrid tissue engineered constructs.

    Science.gov (United States)

    Mekhileri, N V; Lim, K S; Brown, G C J; Mutreja, I; Schon, B S; Hooper, G J; Woodfield, T B F

    2018-01-12

    Bottom-up biofabrication approaches combining micro-tissue fabrication techniques with extrusion-based 3D printing of thermoplastic polymer scaffolds are emerging strategies in tissue engineering. These biofabrication strategies support native self-assembly mechanisms observed in developmental stages of tissue or organoid growth as well as promoting cell-cell interactions and cell differentiation capacity. Few technologies have been developed to automate the precise assembly of micro-tissues or tissue modules into structural scaffolds. We describe an automated 3D bioassembly platform capable of fabricating simple hybrid constructs via a two-step bottom-up bioassembly strategy, as well as complex hybrid hierarchical constructs via a multistep bottom-up bioassembly strategy. The bioassembly system consisted of a fluidic-based singularisation and injection module incorporated into a commercial 3D bioprinter. The singularisation module delivers individual micro-tissues to an injection module, for insertion into precise locations within a 3D plotted scaffold. To demonstrate applicability for cartilage tissue engineering, human chondrocytes were isolated and micro-tissues of 1 mm diameter were generated utilising a high throughput 96-well plate format. Micro-tissues were singularised with an efficiency of 96.0 ± 5.1%. There was no significant difference in size, shape or viability of micro-tissues before and after automated singularisation and injection. A layer-by-layer approach or aforementioned bottom-up bioassembly strategy was employed to fabricate a bilayered construct by alternatively 3D plotting a thermoplastic (PEGT/PBT) polymer scaffold and inserting pre-differentiated chondrogenic micro-tissues or cell-laden gelatin-based (GelMA) hydrogel micro-spheres, both formed via high-throughput fabrication techniques. No significant difference in viability between the construct assembled utilising the automated bioassembly system and manually assembled construct was

  4. Influence of extremely low frequency, low energy electromagnetic fields and combined mechanical stimulation on chondrocytes in 3-D constructs for cartilage tissue engineering.

    Science.gov (United States)

    Hilz, Florian M; Ahrens, Philipp; Grad, Sibylle; Stoddart, Martin J; Dahmani, Chiheb; Wilken, Frauke L; Sauerschnig, Martin; Niemeyer, Philipp; Zwingmann, Jörn; Burgkart, Rainer; von Eisenhart-Rothe, Rüdiger; Südkamp, Norbert P; Weyh, Thomas; Imhoff, Andreas B; Alini, Mauro; Salzmann, Gian M

    2014-02-01

    Articular cartilage, once damaged, has very low regenerative potential. Various experimental approaches have been conducted to enhance chondrogenesis and cartilage maturation. Among those, non-invasive electromagnetic fields have shown their beneficial influence for cartilage regeneration and are widely used for the treatment of non-unions, fractures, avascular necrosis and osteoarthritis. One very well accepted way to promote cartilage maturation is physical stimulation through bioreactors. The aim of this study was the investigation of combined mechanical and electromagnetic stress affecting cartilage cells in vitro. Primary articular chondrocytes from bovine fetlock joints were seeded into three-dimensional (3-D) polyurethane scaffolds and distributed into seven stimulated experimental groups. They either underwent mechanical or electromagnetic stimulation (sinusoidal electromagnetic field of 1 mT, 2 mT, or 3 mT; 60 Hz) or both within a joint-specific bioreactor and a coil system. The scaffold-cell constructs were analyzed for glycosaminoglycan (GAG) and DNA content, histology, and gene expression of collagen-1, collagen-2, aggrecan, cartilage oligomeric matrix protein (COMP), Sox9, proteoglycan-4 (PRG-4), and matrix metalloproteinases (MMP-3 and -13). There were statistically significant differences in GAG/DNA content between the stimulated versus the control group with highest levels in the combined stimulation group. Gene expression was significantly higher for combined stimulation groups versus static control for collagen 2/collagen 1 ratio and lower for MMP-13. Amongst other genes, a more chondrogenic phenotype was noticed in expression patterns for the stimulated groups. To conclude, there is an effect of electromagnetic and mechanical stimulation on chondrocytes seeded in a 3-D scaffold, resulting in improved extracellular matrix production. © 2013 Wiley Periodicals, Inc.

  5. Towards a Constructive Foundation of Quantum Mechanics

    Science.gov (United States)

    Smilga, Walter

    2017-01-01

    I describe a constructive foundation for quantum mechanics, based on the discreteness of the degrees of freedom of quantum objects and on the Principle of Relativity. Taking Einstein's historical construction of Special Relativity as a model, the construction is carried out in close contact with a simple quantum mechanical Gedanken experiment. This leads to the standard axioms of quantum mechanics. The quantum mechanical description is identified as a mathematical tool that allows describing objects, whose degree of freedom in space-time has a discrete spectrum, relative to classical observers in space-time. This description is covariant with respect to (continuous) coordinate transformations and meets the requirement that the spectrum is the same in every inertial system. The construction gives detailed answers to controversial questions, such as the measurement problem, the informational content of the wave function, and the completeness of quantum mechanics.

  6. Nondestructive mechanical characterization of developing biological tissues using inflation testing.

    Science.gov (United States)

    Oomen, P J A; van Kelle, M A J; Oomens, C W J; Bouten, C V C; Loerakker, S

    2017-10-01

    One of the hallmarks of biological soft tissues is their capacity to grow and remodel in response to changes in their environment. Although it is well-accepted that these processes occur at least partly to maintain a mechanical homeostasis, it remains unclear which mechanical constituent(s) determine(s) mechanical homeostasis. In the current study a nondestructive mechanical test and a two-step inverse analysis method were developed and validated to nondestructively estimate the mechanical properties of biological tissue during tissue culture. Nondestructive mechanical testing was achieved by performing an inflation test on tissues that were cultured inside a bioreactor, while the tissue displacement and thickness were nondestructively measured using ultrasound. The material parameters were estimated by an inverse finite element scheme, which was preceded by an analytical estimation step to rapidly obtain an initial estimate that already approximated the final solution. The efficiency and accuracy of the two-step inverse method was demonstrated on virtual experiments of several material types with known parameters. PDMS samples were used to demonstrate the method's feasibility, where it was shown that the proposed method yielded similar results to tensile testing. Finally, the method was applied to estimate the material properties of tissue-engineered constructs. Via this method, the evolution of mechanical properties during tissue growth and remodeling can now be monitored in a well-controlled system. The outcomes can be used to determine various mechanical constituents and to assess their contribution to mechanical homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Mechanics of epithelial tissue homeostasis and morphogenesis.

    Science.gov (United States)

    Guillot, Charlène; Lecuit, Thomas

    2013-06-07

    Epithelia are robust tissues that support the structure of embryos and organs and serve as effective barriers against pathogens. Epithelia also chemically separate different physiological environments. These vital functions require tight association between cells through the assembly of junctions that mechanically stabilize the tissue. Remarkably, epithelia are also dynamic and can display a fluid behavior. Cells continuously die or divide, thereby allowing functional tissue homeostasis. Epithelial cells can change shape or intercalate as tissues deform during morphogenesis. We review the mechanical basis of tissue robustness and fluidity, with an emphasis on the pivotal role of junction dynamics. Tissue fluidity emerges from local active stresses acting at cell interfaces and allows the maintenance of epithelial organization during morphogenesis and tissue renewal.

  8. Lung tissue mechanics as an emergent phenomenon.

    Science.gov (United States)

    Suki, Béla; Bates, Jason H T

    2011-04-01

    The mechanical properties of lung parenchymal tissue are both elastic and dissipative, as well as being highly nonlinear. These properties cannot be fully understood, however, in terms of the individual constituents of the tissue. Rather, the mechanical behavior of lung tissue emerges as a macroscopic phenomenon from the interactions of its microscopic components in a way that is neither intuitive nor easily understood. In this review, we first consider the quasi-static mechanical behavior of lung tissue and discuss computational models that show how smooth nonlinear stress-strain behavior can arise through a percolation-like process in which the sequential recruitment of collagen fibers with increasing strain causes them to progressively take over the load-bearing role from elastin. We also show how the concept of percolation can be used to link the pathologic progression of parenchymal disease at the micro scale to physiological symptoms at the macro scale. We then examine the dynamic mechanical behavior of lung tissue, which invokes the notion of tissue resistance. Although usually modeled phenomenologically in terms of collections of springs and dashpots, lung tissue viscoelasticity again can be seen to reflect various types of complex dynamic interactions at the molecular level. Finally, we discuss the inevitability of why lung tissue mechanics need to be complex.

  9. Mechanical construction of the 22 Nova laser

    International Nuclear Information System (INIS)

    Hurley, C.A.; Frick, F.A.; Patton, H.G.; Bradley, G.; Martos, A.

    1983-01-01

    The Nova laser system for Inertial Confinement Fusion studies at Lawrence Livermore National Laboratory is under construction and will be completed October 1984 with first operations scheduled for 1985. This system is the largest precision opto-mechanical engineering system ever built. Major engineering and subsystems are mechanical, optical, and electrical power. A series of system technologies include alignment, diagnostics, target, frequency conversion, and controls. This paper will only discuss the mechanical system

  10. Mechanical homeostasis regulating adipose tissue volume

    Directory of Open Access Journals (Sweden)

    Svedman Paul

    2007-09-01

    Full Text Available Abstract Background The total body adipose tissue volume is regulated by hormonal, nutritional, paracrine, neuronal and genetic control signals, as well as components of cell-cell or cell-matrix interactions. There are no known locally acting homeostatic mechanisms by which growing adipose tissue might adapt its volume. Presentation of the hypothesis Mechanosensitivity has been demonstrated by mesenchymal cells in tissue culture. Adipocyte differentiation has been shown to be inhibited by stretching in vitro, and a pathway for the response has been elucidated. In humans, intermittent stretching of skin for reconstructional purposes leads to thinning of adipose tissue and thickening of epidermis – findings matching those observed in vitro in response to mechanical stimuli. Furthermore, protracted suspension of one leg increases the intermuscular adipose tissue volume of the limb. These findings may indicate a local homeostatic adipose tissue volume-regulating mechanism based on movement-induced reduction of adipocyte differentiation. This function might, during evolution, have been of importance in confined spaces, where overgrowth of adipose tissue could lead to functional disturbance, as for instance in the turtle. In humans, adipose tissue near muscle might in particular be affected, for instance intermuscularly, extraperitoneally and epicardially. Mechanical homeostasis might also contribute to protracted maintainment of soft tissue shape in the face and neck region. Testing of the hypothesis Assessment of messenger RNA-expression of human adipocytes following activity in adjacent muscle is planned, and study of biochemical and volumetric adipose tissue changes in man are proposed. Implications of the hypothesis The interpretation of metabolic disturbances by means of adipose tissue might be influenced. Possible applications in the head and neck were discussed.

  11. Tissue Equivalents Based on Cell-Seeded Biodegradable Microfluidic Constructs

    Directory of Open Access Journals (Sweden)

    Sarah L. Tao

    2010-03-01

    Full Text Available One of the principal challenges in the field of tissue engineering and regenerative medicine is the formation of functional microvascular networks capable of sustaining tissue constructs. Complex tissues and vital organs require a means to support oxygen and nutrient transport during the development of constructs both prior to and after host integration, and current approaches have not demonstrated robust solutions to this challenge. Here, we present a technology platform encompassing the design, construction, cell seeding and functional evaluation of tissue equivalents for wound healing and other clinical applications. These tissue equivalents are comprised of biodegradable microfluidic scaffolds lined with microvascular cells and designed to replicate microenvironmental cues necessary to generate and sustain cell populations to replace dermal and/or epidermal tissues lost due to trauma or disease. Initial results demonstrate that these biodegradable microfluidic devices promote cell adherence and support basic cell functions. These systems represent a promising pathway towards highly integrated three-dimensional engineered tissue constructs for a wide range of clinical applications.

  12. 3D Bioprinting of Artificial Tissues: Construction of Biomimetic Microstructures.

    Science.gov (United States)

    Luo, Yongxiang; Lin, Xin; Huang, Peng

    2018-04-24

    It is promising that artificial tissues/organs for clinical application can be produced via 3D bioprinting of living cells and biomaterials. The construction of microstructures biomimicking native tissues is crucially important to create artificial tissues with biological functions. For instance, the fabrication of vessel-like networks to supply cells with initial nutrient and oxygen, and the arrangement of multiple types of cells for creating lamellar/complex tissues through 3D bioprinting are widely reported. The current advances in 3D bioprinting of artificial tissues from the view of construction of biomimetic microstructures, especially the fabrication of lamellar, vascular, and complex structures are summarized. In the end, the conclusion and perspective of 3D bioprinting for clinical applications are elaborated. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Mechanical cues in orofacial tissue engineering and regenerative medicine.

    Science.gov (United States)

    Brouwer, Katrien M; Lundvig, Ditte M S; Middelkoop, Esther; Wagener, Frank A D T G; Von den Hoff, Johannes W

    2015-01-01

    Cleft lip and palate patients suffer from functional, aesthetical, and psychosocial problems due to suboptimal regeneration of skin, mucosa, and skeletal muscle after restorative cleft surgery. The field of tissue engineering and regenerative medicine (TE/RM) aims to restore the normal physiology of tissues and organs in conditions such as birth defects or after injury. A crucial factor in cell differentiation, tissue formation, and tissue function is mechanical strain. Regardless of this, mechanical cues are not yet widely used in TE/RM. The effects of mechanical stimulation on cells are not straight-forward in vitro as cellular responses may differ with cell type and loading regime, complicating the translation to a therapeutic protocol. We here give an overview of the different types of mechanical strain that act on cells and tissues and discuss the effects on muscle, and skin and mucosa. We conclude that presently, sufficient knowledge is lacking to reproducibly implement external mechanical loading in TE/RM approaches. Mechanical cues can be applied in TE/RM by fine-tuning the stiffness and architecture of the constructs to guide the differentiation of the seeded cells or the invading surrounding cells. This may already improve the treatment of orofacial clefts and other disorders affecting soft tissues. © 2015 by the Wound Healing Society.

  14. Artificial urinary conduit construction using tissue engineering methods.

    Science.gov (United States)

    Kloskowski, Tomasz; Pokrywczyńska, Marta; Drewa, Tomasz

    2015-01-01

    Incontinent urinary diversion using an ileal conduit is the most popular method used by urologists after bladder cystectomy resulting from muscle invasive bladder cancer. The use of gastrointestinal tissue is related to a series of complications with the necessity of surgical procedure extension which increases the time of surgery. Regenerative medicine together with tissue engineering techniques gives hope for artificial urinary conduit construction de novo without affecting the ileum. In this review we analyzed history of urinary diversion together with current attempts in urinary conduit construction using tissue engineering methods. Based on literature and our own experience we presented future perspectives related to the artificial urinary conduit construction. A small number of papers in the field of tissue engineered urinary conduit construction indicates that this topic requires more attention. Three main factors can be distinguished to resolve this topic: proper scaffold construction along with proper regeneration of both the urothelium and smooth muscle layers. Artificial urinary conduit has a great chance to become the first commercially available product in urology constructed by regenerative medicine methods.

  15. Transient Mechanical Response of Lung Airway Tissue during Mechanical Ventilation

    Directory of Open Access Journals (Sweden)

    Israr Bin Muhammad Ibrahim

    2016-01-01

    Full Text Available Patients with acute lung injury, airway and other pulmonary diseases often require Mechanical Ventilation (MV. Knowledge of the stress/strain environment in lung airway tissues is very important in order to avoid lung injuries for patients undergoing MV. Airway tissue strains responsible for stressing the lung’s fiber network and rupturing the lung due to compliant airways are very difficult to measure experimentally. Multi-level modeling is adopted to investigate the transient mechanical response of the tissue under MV. First, airflow through a lung airway bifurcation (Generation 4–6 is modeled using Computational Fluid Dynamics (CFD to obtain air pressure during 2 seconds of MV breathing. Next, the transient air pressure was used in structural analysis to obtain mechanical strain experienced by the airway tissue wall. Structural analysis showed that airway tissue from Generation 5 in one bifurcation can stretch eight times that of airway tissue of the same generation number but with different bifurcation. The results suggest sensitivity of load to geometrical features. Furthermore, the results of strain levels obtained from the tissue analysis are very important because these strains at the cellular-level can create inflammatory responses, thus damaging the airway tissues.

  16. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

    Science.gov (United States)

    Elomaa, Laura; Yang, Yunzhi Peter

    2017-10-01

    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  17. Tissue microarray construction for salivary gland tumors study

    Science.gov (United States)

    Paiva-Fonseca, Felipe; de-Almeida, Oslei P.; Ayroza-Rangel, Ana L C.

    2013-01-01

    Objective: To describe and discuss the design, building and usefulness of tissue microarray (TMA) blocks for the study of salivary gland tumors (SGTs). Study Design: Two hundred thirty-eight formalin-fixed, paraffin-embedded SGTs were arranged in blocks of TMA using a manual tissue arrayer. Three representative cores of 1.0, 2.0 or 3.0mm were taken from each original block and their characteristics were analyzed and described. Results: It was created 12 TMA blocks that presented highly representative neoplastic cylinders. However, those neoplasias rich in cystic spaces such as mucoepidermoid carcinoma and Warthin tumor presented more difficulties to be sampled, as the neoplastic tissue available was scarce. Tissue damage and loss during TMA construction was estimated as 3.7%. Conclusion: Representative areas of SGTs, with relatively small loss of tissue, can be obtained with the construction of TMA blocks for molecular studies. However, tumors rich in cystic spaces present more difficulties to be adequately sampled. Key words:Tissue microarray, tma, salivary gland tumors, immunohistochemistry. PMID:22926480

  18. Cryopreservation of Cell/Scaffold Tissue-Engineered Constructs

    Science.gov (United States)

    Costa, Pedro F.; Dias, Ana F.; Reis, Rui L.

    2012-01-01

    The aim of this work was to study the effect of cryopreservation over the functionality of tissue-engineered constructs, analyzing the survival and viability of cells seeded, cultured, and cryopreserved onto 3D scaffolds. Further, it also evaluated the effect of cryopreservation over the properties of the scaffold material itself since these are critical for the engineering of most tissues and in particular, tissues such as bone. For this purpose, porous scaffolds, namely fiber meshes based on a starch and poly(caprolactone) blend were seeded with goat bone marrow stem cells (GBMSCs) and cryopreserved for 7 days. Discs of the same material seeded with GBMSCs were also used as controls. After this period, these samples were analyzed and compared to samples collected before the cryopreservation process. The obtained results demonstrate that it is possible to maintain cell viability and scaffolds properties upon cryopreservation of tissue-engineered constructs based on starch scaffolds and goat bone marrow mesenchymal cells using standard cryopreservation methods. In addition, the outcomes of this study suggest that the greater porosity and interconnectivity of scaffolds favor the retention of cellular content and cellular viability during cryopreservation processes, when compared with nonporous discs. These findings indicate that it might be possible to prepare off-the-shelf engineered tissue substitutes and preserve them to be immediately available upon request for patients' needs. PMID:22676448

  19. Additive manufacturing techniques for the production of tissue engineering constructs.

    Science.gov (United States)

    Mota, Carlos; Puppi, Dario; Chiellini, Federica; Chiellini, Emo

    2015-03-01

    'Additive manufacturing' (AM) refers to a class of manufacturing processes based on the building of a solid object from three-dimensional (3D) model data by joining materials, usually layer upon layer. Among the vast array of techniques developed for the production of tissue-engineering (TE) scaffolds, AM techniques are gaining great interest for their suitability in achieving complex shapes and microstructures with a high degree of automation, good accuracy and reproducibility. In addition, the possibility of rapidly producing tissue-engineered constructs meeting patient's specific requirements, in terms of tissue defect size and geometry as well as autologous biological features, makes them a powerful way of enhancing clinical routine procedures. This paper gives an extensive overview of different AM techniques classes (i.e. stereolithography, selective laser sintering, 3D printing, melt-extrusion-based techniques, solution/slurry extrusion-based techniques, and tissue and organ printing) employed for the development of tissue-engineered constructs made of different materials (i.e. polymeric, ceramic and composite, alone or in combination with bioactive agents), by highlighting their principles and technological solutions. Copyright © 2012 John Wiley & Sons, Ltd.

  20. The Expanding World of Tissue Engineering: The Building Blocks and New Applications of Tissue Engineered Constructs

    Science.gov (United States)

    Zorlutuna, Pinar; Vrana, Nihal Engin; Khademhosseini, Ali

    2013-01-01

    The field of tissue engineering has been growing in the recent years as more products have made it to the market and as new uses for the engineered tissues have emerged, motivating many researchers to engage in this multidisciplinary field of research. Engineered tissues are now not only considered as end products for regenerative medicine, but also have emerged as enabling technologies for other fields of research ranging from drug discovery to biorobotics. This widespread use necessitates a variety of methodologies for production of tissue engineered constructs. In this review, these methods together with their non-clinical applications will be described. First, we will focus on novel materials used in tissue engineering scaffolds; such as recombinant proteins and synthetic, self assembling polypeptides. The recent advances in the modular tissue engineering area will be discussed. Then scaffold-free production methods, based on either cell sheets or cell aggregates will be described. Cell sources used in tissue engineering and new methods that provide improved control over cell behavior such as pathway engineering and biomimetic microenvironments for directing cell differentiation will be discussed. Finally, we will summarize the emerging uses of engineered constructs such as model tissues for drug discovery, cancer research and biorobotics applications. PMID:23268388

  1. [Research progress of co-culture system for constructing vascularized tissue engineered bone].

    Science.gov (United States)

    Fu, Weili; Xiang, Zhou

    2014-02-01

    To review the research progress of the co-culture system for constructing vascularized tissue engineered bone. The recent literature concerning the co-culture system for constructing vascularized tissue engineered bone was reviewed, including the selection of osteogenic and endothelial lineages, the design and surface modification of scaffolds, the models and dimensions of the co-culture system, the mechanism, the culture conditions, and their application progress. The construction of vascularized tissue engineered bone is the prerequisite for their survival and further clinical application in vivo. Mesenchymal stem cells (owning the excellent osteogenic potential) and endothelial progenitor cells (capable of directional differentiation into endothelial cell) are considered as attractive cell types for the co-culture system to construct vascularized tissue engineered bone. The culture conditions need to be further optimized. Furthermore, how to achieve the clinical goals of minimal invasion and autologous transplantation also need to be further studied. The strategy of the co-culture system for constructing vascularized tissue engineered bone would have a very broad prospects for clinical application in future.

  2. Mechanisms of lymphatic regeneration after tissue transfer.

    Directory of Open Access Journals (Sweden)

    Alan Yan

    2011-02-01

    Full Text Available Lymphedema is the chronic swelling of an extremity that occurs commonly after lymph node resection for cancer treatment. Recent studies have demonstrated that transfer of healthy tissues can be used as a means of bypassing damaged lymphatics and ameliorating lymphedema. The purpose of these studies was to investigate the mechanisms that regulate lymphatic regeneration after tissue transfer.Nude mice (recipients underwent 2-mm tail skin excisions that were either left open or repaired with full-thickness skin grafts harvested from donor transgenic mice that expressed green fluorescent protein in all tissues or from LYVE-1 knockout mice. Lymphatic regeneration, expression of VEGF-C, macrophage infiltration, and potential for skin grafting to bypass damaged lymphatics were assessed.Skin grafts healed rapidly and restored lymphatic flow. Lymphatic regeneration occurred beginning at the peripheral edges of the graft, primarily from ingrowth of new lymphatic vessels originating from the recipient mouse. In addition, donor lymphatic vessels appeared to spontaneously re-anastomose with recipient vessels. Patterns of VEGF-C expression and macrophage infiltration were temporally and spatially associated with lymphatic regeneration. When compared to mice treated with excision only, there was a 4-fold decrease in tail volumes, 2.5-fold increase in lymphatic transport by lymphoscintigraphy, 40% decrease in dermal thickness, and 54% decrease in scar index in skin-grafted animals, indicating that tissue transfer could bypass damaged lymphatics and promote rapid lymphatic regeneration.Our studies suggest that lymphatic regeneration after tissue transfer occurs by ingrowth of lymphatic vessels and spontaneous re-connection of existing lymphatics. This process is temporally and spatially associated with VEGF-C expression and macrophage infiltration. Finally, tissue transfer can be used to bypass damaged lymphatics and promote rapid lymphatic regeneration.

  3. Mechanisms of glucose uptake in cancer tissue

    International Nuclear Information System (INIS)

    Chung, June Key

    1999-01-01

    Cancer cells are known to show increased rates of glycolysis metabolism. Based on this, PET studies using F-18-fluorodeoxyglucose have been used for the detection of primary and metastatic tumors. To account for this increased glucose uptake, a variety of mechanisms has been proposed. Glucose influx across the cell membrane is mediated by a family of structurally related proteins known as glucose transporters (Gluts). Among 6 isoforms of Gluts, Glut-1 and/or Glut-3 have been reported to show increased expression in various tumors. Increased level of Glut mRNA transcription is supposed to be the basic mechanism of Glut overexpression at the protein level. Some oncogens such as src or ras intensely stimulate Glut-1 by means of increased Glut-1 mRNA levels. Hexokinase activity is another important factor in glucose uptake in cancer cells. Especially hexokinase type II is considered to be involved in glycolysis of cancer cells. Much of the hexokinase of tumor cells is bound to outer membrane of mitochondria by the porin, a hexokinase receptor. Through this interaction, hexokinase may gain preferred access to ATP synthesized via oxidative phosphorylation in the inner mitochondria compartment. Other biologic factors such as tumor blood flow, blood volume, hypoxia, and infiltrating cells in tumor tissue are involved. Relative hypoxia may activate the anaerobic glycolytic pathway. Surrounding macrophages and newly formed granulation tissue in tumor showed greater glucose uptake than did viable cancer cells. To expand the application on FDG PET in oncology, it is important for nuclear medicine physicians to understand the related mechanisms of glucose uptake in cancer tissue

  4. A new construction technique for tissue-engineered heart valves using the self-assembly method.

    Science.gov (United States)

    Tremblay, Catherine; Ruel, Jean; Bourget, Jean-Michel; Laterreur, Véronique; Vallières, Karine; Tondreau, Maxime Y; Lacroix, Dan; Germain, Lucie; Auger, François A

    2014-11-01

    Tissue engineering appears as a promising option to create new heart valve substitutes able to overcome the serious drawbacks encountered with mechanical substitutes or tissue valves. The objective of this article is to present the construction method of a new entirely biological stentless aortic valve using the self-assembly method and also a first assessment of its behavior in a bioreactor when exposed to a pulsatile flow. A thick tissue was created by stacking several fibroblast sheets produced with the self-assembly technique. Different sets of custom-made templates were designed to confer to the thick tissue a three-dimensional (3D) shape similar to that of a native aortic valve. The construction of the valve was divided in two sequential steps. The first step was the installation of the thick tissue in a flat preshaping template followed by a 4-week maturation period. The second step was the actual cylindrical 3D forming of the valve. The microscopic tissue structure was assessed using histological cross sections stained with Masson's Trichrome and Picrosirius Red. The thick tissue remained uniformly populated with cells throughout the construction steps and the dense extracellular matrix presented corrugated fibers of collagen. This first prototype of tissue-engineered heart valve was installed in a bioreactor to assess its capacity to sustain a light pulsatile flow at a frequency of 0.5 Hz. Under the light pulsed flow, it was observed that the leaflets opened and closed according to the flow variations. This study demonstrates that the self-assembly method is a viable option for the construction of complex 3D shapes, such as heart valves, with an entirely biological material.

  5. Overview on Techniques to Construct Tissue Arrays with Special Emphasis on Tissue Microarrays

    Science.gov (United States)

    Vogel, Ulrich

    2014-01-01

    With the advent of new histopathological staining techniques (histochemistry, immunohistochemistry, in situ hybridization) and the discovery of thousands of new genes, mRNA, and proteins by molecular biology, the need grew for a technique to compare many different cells or tissues on one slide in a cost effective manner and with the possibility to easily track the identity of each specimen: the tissue array (TA). Basically, a TA consists of at least two different specimens per slide. TAs differ in the kind of specimens, the number of specimens installed, the dimension of the specimens, the arrangement of the specimens, the embedding medium, the technique to prepare the specimens to be installed, and the technique to construct the TA itself. A TA can be constructed by arranging the tissue specimens in a mold and subsequently pouring the mold with the embedding medium of choice. In contrast, preformed so-called recipient blocks consisting of the embedding medium of choice have punched, drilled, or poured holes of different diameters and distances in which the cells or tissue biopsies will be deployed manually, semi-automatically, or automatically. The costs of constructing a TA differ from a few to thousands of Euros depending on the technique/equipment used. Remarkably high quality TAs can be also achieved by low cost techniques. PMID:27600339

  6. A high throughput mechanical screening device for cartilage tissue engineering.

    Science.gov (United States)

    Mohanraj, Bhavana; Hou, Chieh; Meloni, Gregory R; Cosgrove, Brian D; Dodge, George R; Mauck, Robert L

    2014-06-27

    Articular cartilage enables efficient and near-frictionless load transmission, but suffers from poor inherent healing capacity. As such, cartilage tissue engineering strategies have focused on mimicking both compositional and mechanical properties of native tissue in order to provide effective repair materials for the treatment of damaged or degenerated joint surfaces. However, given the large number design parameters available (e.g. cell sources, scaffold designs, and growth factors), it is difficult to conduct combinatorial experiments of engineered cartilage. This is particularly exacerbated when mechanical properties are a primary outcome, given the long time required for testing of individual samples. High throughput screening is utilized widely in the pharmaceutical industry to rapidly and cost-effectively assess the effects of thousands of compounds for therapeutic discovery. Here we adapted this approach to develop a high throughput mechanical screening (HTMS) system capable of measuring the mechanical properties of up to 48 materials simultaneously. The HTMS device was validated by testing various biomaterials and engineered cartilage constructs and by comparing the HTMS results to those derived from conventional single sample compression tests. Further evaluation showed that the HTMS system was capable of distinguishing and identifying 'hits', or factors that influence the degree of tissue maturation. Future iterations of this device will focus on reducing data variability, increasing force sensitivity and range, as well as scaling-up to even larger (96-well) formats. This HTMS device provides a novel tool for cartilage tissue engineering, freeing experimental design from the limitations of mechanical testing throughput. © 2013 Published by Elsevier Ltd.

  7. Magnetic nanoparticle-loaded alginate beads for local micro-actuation of in vitro tissue constructs.

    Science.gov (United States)

    Alshehri, Awatef M; Wilson, Otto C; Dahal, Bishnu; Philip, John; Luo, Xiaolong; Raub, Christopher B

    2017-11-01

    Magnetic nanoparticles (MNPs) self-align and transduce magnetic force, two properties which lead to promising applications in cell and tissue engineering. However, the toxicity of MNPs to cells which uptake them is a major impediment to applications in engineered tissue constructs. To address this problem, MNPs were embedded in millimeter-scale alginate beads, coated with glutaraldehyde cross-linked chitosan, and loaded in acellular and MDA-MB-231 cancer cell-seeded collagen hydrogels, providing local micro-actuation under an external magnetic field. Brightfield microscopy was used to assess nanoparticle diffusion from the bead. Phase contrast microscopy and digital image correlation were used to track collagen matrix displacement and estimate intratissue strain under magnetic actuation. Coating the magnetic alginate beads with glutaraldehyde-chitosan prevents bulk diffusion of nanoparticles into the surrounding microenvironment. Further, the beads exert force on the surrounding collagen gel and cells, resulting in intratissue strains of 0-10% tunable with bead dimensions, collagen density, and distance from the bead. Cells seeded adjacent to the embedded beads are subjected to strain gradients without loss of cell viability over two days culture. This study describes a simple way to fabricate crosslinked magnetic alginate beads to load in a collagen tissue construct without direct exposure of the construct to nanoparticles. The findings are significant to in vitro studies of mechanobiology in enabling precise control over dynamic mechanical loading of tissue constructs. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Reaction Mechanism Generator: Automatic construction of chemical kinetic mechanisms

    Science.gov (United States)

    Gao, Connie W.; Allen, Joshua W.; Green, William H.; West, Richard H.

    2016-06-01

    Reaction Mechanism Generator (RMG) constructs kinetic models composed of elementary chemical reaction steps using a general understanding of how molecules react. Species thermochemistry is estimated through Benson group additivity and reaction rate coefficients are estimated using a database of known rate rules and reaction templates. At its core, RMG relies on two fundamental data structures: graphs and trees. Graphs are used to represent chemical structures, and trees are used to represent thermodynamic and kinetic data. Models are generated using a rate-based algorithm which excludes species from the model based on reaction fluxes. RMG can generate reaction mechanisms for species involving carbon, hydrogen, oxygen, sulfur, and nitrogen. It also has capabilities for estimating transport and solvation properties, and it automatically computes pressure-dependent rate coefficients and identifies chemically-activated reaction paths. RMG is an object-oriented program written in Python, which provides a stable, robust programming architecture for developing an extensible and modular code base with a large suite of unit tests. Computationally intensive functions are cythonized for speed improvements.

  9. A hyaluronan-based scaffold for the in vitro construction of dental pulp-like tissue.

    Science.gov (United States)

    Ferroni, Letizia; Gardin, Chiara; Sivolella, Stefano; Brunello, Giulia; Berengo, Mario; Piattelli, Adriano; Bressan, Eriberto; Zavan, Barbara

    2015-03-02

    Dental pulp tissue supports the vitality of the tooth, but it is particularly vulnerable to external insults, such as mechanical trauma, chemical irritation or microbial invasion, which can lead to tissue necrosis. In the present work, we present an endodontic regeneration method based on the use of a tridimensional (3D) hyaluronan scaffold and human dental pulp stem cells (DPSCs) to produce a functional dental pulp-like tissue in vitro. An enriched population of DPSCs was seeded onto hyaluronan-based non-woven meshes in the presence of differentiation factors to induce the commitment of stem cells to neuronal, glial, endothelial and osteogenic phenotypes. In vitro experiments, among which were gene expression profiling and immunofluorescence (IF) staining, proved the commitment of DPSCs to the main components of dental pulp tissue. In particular, the hyaluronan-DPSCs construct showed a dental pulp-like morphology consisting of several specialized cells growing inside the hyaluronan fibers. Furthermore, these constructs were implanted into rat calvarial critical-size defects. Histological analyses and gene expression profiling performed on hyaluronan-DPSCs grafts showed the regeneration of osteodentin-like tissue. Altogether, these data suggest the regenerative potential of the hyaluronan-DPSC engineered tissue.

  10. A Hyaluronan-Based Scaffold for the in Vitro Construction of Dental Pulp-Like Tissue

    Directory of Open Access Journals (Sweden)

    Letizia Ferroni

    2015-03-01

    Full Text Available Dental pulp tissue supports the vitality of the tooth, but it is particularly vulnerable to external insults, such as mechanical trauma, chemical irritation or microbial invasion, which can lead to tissue necrosis. In the present work, we present an endodontic regeneration method based on the use of a tridimensional (3D hyaluronan scaffold and human dental pulp stem cells (DPSCs to produce a functional dental pulp-like tissue in vitro. An enriched population of DPSCs was seeded onto hyaluronan-based non-woven meshes in the presence of differentiation factors to induce the commitment of stem cells to neuronal, glial, endothelial and osteogenic phenotypes. In vitro experiments, among which were gene expression profiling and immunofluorescence (IF staining, proved the commitment of DPSCs to the main components of dental pulp tissue. In particular, the hyaluronan-DPSCs construct showed a dental pulp-like morphology consisting of several specialized cells growing inside the hyaluronan fibers. Furthermore, these constructs were implanted into rat calvarial critical-size defects. Histological analyses and gene expression profiling performed on hyaluronan-DPSCs grafts showed the regeneration of osteodentin-like tissue. Altogether, these data suggest the regenerative potential of the hyaluronan-DPSC engineered tissue.

  11. Mechanics of needle-tissue interaction

    NARCIS (Netherlands)

    Roesthuis, Roy; van Veen, Youri; Jahya, Alex; Misra, Sarthak

    2011-01-01

    When a needle is inserted into soft tissue, interac- tion forces are developed at the needle tip and along the needle shaft. The needle tip force is due to cutting of the tissue, and the force along the needle shaft is due to friction between needle and tissue. In this study, the friction force is

  12. Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering.

    Science.gov (United States)

    Nims, Robert J; Durney, Krista M; Cigan, Alexander D; Dusséaux, Antoine; Hung, Clark T; Ateshian, Gerard A

    2016-02-06

    This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process.

  13. Gold nanorod-incorporated gelatin-based conductive hydrogels for engineering cardiac tissue constructs.

    Science.gov (United States)

    Navaei, Ali; Saini, Harpinder; Christenson, Wayne; Sullivan, Ryan Tanner; Ros, Robert; Nikkhah, Mehdi

    2016-09-01

    The development of advanced biomaterials is a crucial step to enhance the efficacy of tissue engineering strategies for treatment of myocardial infarction. Specific characteristics of biomaterials including electrical conductivity, mechanical robustness and structural integrity need to be further enhanced to promote the functionalities of cardiac cells. In this work, we fabricated UV-crosslinkable gold nanorod (GNR)-incorporated gelatin methacrylate (GelMA) hybrid hydrogels with enhanced material and biological properties for cardiac tissue engineering. Embedded GNRs promoted electrical conductivity and mechanical stiffness of the hydrogel matrix. Cardiomyocytes seeded on GelMA-GNR hybrid hydrogels exhibited excellent cell retention, viability, and metabolic activity. The increased cell adhesion resulted in abundance of locally organized F-actin fibers, leading to the formation of an integrated tissue layer on the GNR-embedded hydrogels. Immunostained images of integrin β-1 confirmed improved cell-matrix interaction on the hybrid hydrogels. Notably, homogeneous distribution of cardiac specific markers (sarcomeric α-actinin and connexin 43), were observed on GelMA-GNR hydrogels as a function of GNRs concentration. Furthermore, the GelMA-GNR hybrids supported synchronous tissue-level beating of cardiomyocytes. Similar observations were also noted by, calcium transient assay that demonstrated the rhythmic contraction of the cardiomyocytes on GelMA-GNR hydrogels as compared to pure GelMA. Thus, the findings of this study clearly demonstrated that functional cardiac patches with superior electrical and mechanical properties can be developed using nanoengineered GelMA-GNR hybrid hydrogels. In this work, we developed gold nanorod (GNR) incorporated gelatin-based hydrogels with suitable electrical conductivity and mechanical stiffness for engineering functional cardiac tissue constructs (e.g. cardiac patches). The synthesized conductive hybrid hydrogels properly

  14. Stimulating angiogenesis by hyperbaric oxygen in an isolated tissue construct.

    Science.gov (United States)

    Roth, Valerie; Herron, Margo S; Bueno, Reuben A; Chambers, Christopher B; Neumeister, Michael W

    2011-01-01

    Hyperbaric oxygen (HBO2) treatment has been shown to stimulate angiogenesis in prefabricated myocutaneous flaps. We conducted the current study to determine optimal HBO2 treatment intervals for peak angiogenesis. Lewis rats were implanted subcutaneously with silicone molds in the inguinal region. Molds contained inguinal fat, a vascular pedicle and Matrigel plug. Thirty-two animals were randomized into four groups: HBO2 Treatment (2.5 atm of 100% oxygen, 90 minutes, 2x/day)--Group 1 (seven days) or--Group 2 (14 days); and Control Treatment (room air at atmospheric pressure)--Group 1 (seven days) or--Group 2(14 days). Implants were harvested, processed for H&E staining, and imaged digitally; angiogenesis was assessed by grade of vascularization at the Matrigel/fat boundary. Intergroup grading differences were assessed statistically. Vascularization in seven-day HBO2-treated implants was significantly increased compared to seven-day controls (p = 0.008). Vascularization in 14-day HBO2-treated implants was significantly decreased compared to 14-day controls (p = 0.012). There was no significant difference between seven-day HBO-treated implants and 14-day controls (p > 0.05). Short-term HBO2 exposure appears to increase angiogenesis in isolated tissue constructs. Prolonged HBO2 exposure may lead to vascular pruning. Short-term HBO2 exposure appears to expedite the natural vascularization process, resulting in equivalent vascularization in a shorter time.

  15. Masonry constructions mechanical models and numerical applications

    CERN Document Server

    Lucchesi, Massimiliano; Padovani, Cristina

    2008-01-01

    Numerical methods for the structural analysis of masonry constructions can be of great value in assessing the safety of artistically important masonry buildings and optimizing potential operations of maintenance and strengthening in terms of their cost-effectiveness, architectural impact and static effectiveness. This monograph firstly provides a detailed description of the constitutive equation of masonry-like materials, clearly setting out its most important features. It then goes on to provide a numerical procedure to solve the equilibrium problem of masonry solids. A large portion of the w

  16. Crosstalk between Substrates and Rho-Associated Kinase Inhibitors in Cryopreservation of Tissue-Engineered Constructs

    Directory of Open Access Journals (Sweden)

    Arindam Bit

    2017-01-01

    Full Text Available It is documented that human mesenchymal stem cells (hMSCs can be differentiated into various types of cells to present a tool for tissue engineering and regenerative medicine. Thus, the preservation of stem cells is a crucial factor for their effective long-term storage that further facilitates their continuous supply and transportation for application in regenerative medicine. Cryopreservation is the most important, practicable, and the only established mechanism for long-term preservation of cells, tissues, and organs, and engineered tissues; thus, it is the key step for the improvement of tissue engineering. A significant portion of MSCs loses cellular viability while freeze-thawing, which represents an important technical limitation to achieving sufficient viable cell numbers for maximum efficacy. Several natural and synthetic materials are extensively used as substrates for tissue engineering constructs and cryopreservation because they promote cell attachment and proliferation. Rho-associated kinase (ROCK inhibitors can improve the physiological function and postthaw viability of cryopreserved MSCs. This review proposes a crosstalk between substrate topology and interaction of cells with ROCK inhibitors. It is shown that incorporation of ionic nanoparticles in the presence of an external electrical field improves the generation of ROCK inhibitors to safeguard cellular viability for the enhanced cryopreservation of engineered tissues.

  17. Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering.

    Science.gov (United States)

    Nerurkar, Nandan L; Elliott, Dawn M; Mauck, Robert L

    2007-08-01

    Engineering a functional replacement for the annulus fibrosus (AF) of the intervertebral disc is contingent upon recapitulation of AF structure, composition, and mechanical properties. In this study, we propose a new paradigm for AF tissue engineering that focuses on the reconstitution of anatomic fiber architecture and uses constitutive modeling to evaluate construct function. A modified electrospinning technique was utilized to generate aligned nanofibrous polymer scaffolds for engineering the basic functional unit of the AF, a single lamella. Scaffolds were tested in uniaxial tension at multiple fiber orientations, demonstrating a nonlinear dependence of modulus on fiber angle that mimicked the nonlinearity and anisotropy of native AF. A homogenization model previously applied to native AF successfully described scaffold mechanical response, and parametric studies demonstrated that nonfibrillar matrix, along with fiber connectivity, are key contributors to tensile mechanics for engineered AF. We demonstrated that AF cells orient themselves along the aligned scaffolds and deposit matrix that contributes to construct mechanics under loading conditions relevant to the in vivo environment. The homogenization model was applied to cell-seeded constructs and provided quantitative measures for the evolution of matrix and interfibrillar interactions. Finally, the model demonstrated that at fiber angles of the AF (28 degrees -44 degrees ), engineered material behaved much like native tissue, suggesting that engineered constructs replicate the physiologic behavior of the single AF lamella. Constitutive modeling provides a powerful tool for analysis of engineered AF neo-tissue and native AF tissue alike, highlighting key mechanical design criteria for functional AF tissue engineering.

  18. From cells to tissue: A continuum model of epithelial mechanics

    Science.gov (United States)

    Ishihara, Shuji; Marcq, Philippe; Sugimura, Kaoru

    2017-08-01

    A two-dimensional continuum model of epithelial tissue mechanics was formulated using cellular-level mechanical ingredients and cell morphogenetic processes, including cellular shape changes and cellular rearrangements. This model incorporates stress and deformation tensors, which can be compared with experimental data. Focusing on the interplay between cell shape changes and cell rearrangements, we elucidated dynamical behavior underlying passive relaxation, active contraction-elongation, and tissue shear flow, including a mechanism for contraction-elongation, whereby tissue flows perpendicularly to the axis of cell elongation. This study provides an integrated scheme for the understanding of the orchestration of morphogenetic processes in individual cells to achieve epithelial tissue morphogenesis.

  19. Heritable Genetic Changes in Cells Recovered From Irradiated 3D Tissue Constructs

    Energy Technology Data Exchange (ETDEWEB)

    Michael Cornforth

    2012-03-26

    Combining contemporary cytogenetic methods with DNA CGH microarray technology and chromosome flow-sorting increases substantially the ability to resolve exchange breakpoints associated with interstitial deletions and translocations, allowing the consequences of radiation damage to be directly measured at low doses, while also providing valuable insights into molecular mechanisms of misrepair processes that, in turn, identify appropriate biophysical models of risk at low doses. Specific aims apply to cells recovered from 3D tissue constructs of human skin and, for the purpose of comparison, the same cells irradiated in traditional 2D cultures. The project includes research complementary to NASA/HRP space radiation project.

  20. From static to animated: Measuring mechanical forces in tissues.

    Science.gov (United States)

    Nelson, Celeste M

    2017-01-02

    Cells are physical objects that exert mechanical forces on their surroundings as they migrate and take their places within tissues. New techniques are now poised to enable the measurement of cell-generated mechanical forces in intact tissues in vivo, which will illuminate the secret dynamic lives of cells and change our current perception of cell biology. © 2017 Nelson.

  1. A toolbox to explore the mechanics of living embryonic tissues.

    Science.gov (United States)

    Campàs, Otger

    2016-07-01

    The sculpting of embryonic tissues and organs into their functional morphologies involves the spatial and temporal regulation of mechanics at cell and tissue scales. Decades of in vitro work, complemented by some in vivo studies, have shown the relevance of mechanical cues in the control of cell behaviors that are central to developmental processes, but the lack of methodologies enabling precise, quantitative measurements of mechanical cues in vivo have hindered our understanding of the role of mechanics in embryonic development. Several methodologies are starting to enable quantitative studies of mechanics in vivo and in situ, opening new avenues to explore how mechanics contributes to shaping embryonic tissues and how it affects cell behavior within developing embryos. Here we review the present methodologies to study the role of mechanics in living embryonic tissues, considering their strengths and drawbacks as well as the conditions in which they are most suitable. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. A toolbox to explore the mechanics of living embryonic tissues

    Science.gov (United States)

    Campàs, Otger

    2016-01-01

    The sculpting of embryonic tissues and organs into their functional morphologies involves the spatial and temporal regulation of mechanics at cell and tissue scales. Decades of in vitro work, complemented by some in vivo studies, have shown the relevance of mechanical cues in the control of cell behaviors that are central to developmental processes, but the lack of methodologies enabling precise, quantitative measurements of mechanical cues in vivo have hindered our understanding of the role of mechanics in embryonic development. Several methodologies are starting to enable quantitative studies of mechanics in vivo and in situ, opening new avenues to explore how mechanics contributes to shaping embryonic tissues and how it affects cell behavior within developing embryos. Here we review the present methodologies to study the role of mechanics in living embryonic tissues, considering their strengths and drawbacks as well as the conditions in which they are most suitable. PMID:27061360

  3. Effects of tissue mechanical properties on susceptibility to histotripsy-induced tissue damage

    Science.gov (United States)

    Vlaisavljevich, Eli; Kim, Yohan; Owens, Gabe; Roberts, William; Cain, Charles; Xu, Zhen

    2014-01-01

    Histotripsy is a non-invasive tissue ablation method capable of fractionating tissue by controlling acoustic cavitation. To determine the fractionation susceptibility of various tissues, we investigated histotripsy-induced damage on tissue phantoms and ex vivo tissues with different mechanical strengths. A histotripsy bubble cloud was formed at tissue phantom surfaces using 5-cycle long ultrasound pulses with peak negative pressure of 18 MPa and PRFs of 10, 100, and 1000 Hz. Results showed significantly smaller lesions were generated in tissue phantoms of higher mechanical strength. Histotripsy was also applied to 43 different ex vivo porcine tissues with a wide range of mechanical properties. Gross morphology demonstrated stronger tissues with higher ultimate stress, higher density, and lower water content were more resistant to histotripsy damage in comparison to weaker tissues. Based on these results, a self-limiting vessel-sparing treatment strategy was developed in an attempt to preserve major vessels while fractionating the surrounding target tissue. This strategy was tested in porcine liver in vivo. After treatment, major hepatic blood vessels and bile ducts remained intact within a completely fractionated liver volume. These results identify varying susceptibilities of tissues to histotripsy therapy and provide a rational basis to optimize histotripsy parameters for treatment of specific tissues.

  4. Myocardial scaffold-based cardiac tissue engineering: application of coordinated mechanical and electrical stimulations.

    Science.gov (United States)

    Wang, Bo; Wang, Guangjun; To, Filip; Butler, J Ryan; Claude, Andrew; McLaughlin, Ronald M; Williams, Lakiesha N; de Jongh Curry, Amy L; Liao, Jun

    2013-09-03

    Recently, we developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserve the natural extracellular matrix structure, mechanical anisotropy, and vasculature templates and also show good cell recellularization and differentiation potential. In this study, a multistimulation bioreactor was built to provide coordinated mechanical and electrical stimulation for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (10(6) cells/mL) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols. We found that after 2 days of culturing with mechanical (20% strain) and electrical stimulation (5 V, 1 Hz), high cell density and good cell viability were observed in the reseeded scaffold. Immunofluorescence staining demonstrated that the differentiated cells showed a cardiomyocyte-like phenotype by expressing sarcomeric α-actinin, myosin heavy chain, cardiac troponin T, connexin-43, and N-cadherin. Biaxial mechanical testing demonstrated that positive tissue remodeling took place after 2 days of bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2 day and 4 day tissue constructs were comparable to those of the tissue constructs produced by stirring reseeding followed by 2 weeks of static culturing, implying the effectiveness and efficiency of the coordinated simulations in promoting tissue remodeling. In short, the synergistic stimulations might be beneficial not only for the quality of cardiac construct development but also for patients by reducing the waiting time in future clinical scenarios.

  5. Hypoxia induces near-native mechanical properties in engineered heart valve tissue.

    Science.gov (United States)

    Balguid, Angelique; Mol, Anita; van Vlimmeren, Marijke A A; Baaijens, Frank P T; Bouten, Carlijn V C

    2009-01-20

    Previous attempts in heart valve tissue engineering (TE) failed to produce autologous valve replacements with native-like mechanical behavior to allow for systemic pressure applications. Because hypoxia and insulin are known to promote protein synthesis by adaptive cellular responses, a physiologically relevant oxygen tension and insulin supplements were applied to the growing heart valve tissues to enhance their mechanical properties. Scaffolds of rapid-degrading polyglycolic acid meshes coated with poly-4-hydroxybutyrate were seeded with human saphenous vein myofibroblasts. The tissue-engineered constructs were cultured under normal oxygen tension (normoxia) or hypoxia (7% O(2)) and incubated with or without insulin. Glycosaminoglycan production in the constructs approached that of native values under the influence of hypoxia and under the influence of insulin. Both insulin and hypoxia were associated with enhanced matrix production and improved mechanical properties; however, a synergistic effect was not observed. Although the amount of collagen and cross-links in the engineered tissues was still lower than that in native adult human aortic valves, constructs cultured under hypoxic conditions reached native human aortic valve levels of tissue strength and stiffness after 4 weeks of culturing. These results indicate that oxygen tension may be a key parameter for the achievement of sufficient tissue quality and mechanical integrity in tissue-engineered heart valves. Engineered tissues of such strength, based on rapid-degrading polymers, have not been achieved to date. These findings bring the potential use of tissue-engineered heart valves for systemic applications a step closer and represent an important improvement in heart valve tissue engineering.

  6. A Guide for Using Mechanical Stimulation to Enhance Tissue-Engineered Articular Cartilage Properties.

    Science.gov (United States)

    Salinas, Evelia Y; Hu, Jerry C; Athanasiou, Kyriacos A

    2018-03-21

    The use of tissue-engineered articular cartilage (AC) constructs has the potential to become a powerful treatment option for cartilage lesions resulting from trauma or early stages of pathology. Although fundamental tissue-engineering strategies based on the use of scaffolds, cells, and signals have been developed, techniques that lead to biomimetic AC constructs that can be translated to in-vivo use have yet to be fully confirmed. Mechanical stimulation during tissue culture can be an effective strategy to enhance the mechanical, structural, and cellular properties of tissue-engineered constructs toward mimicking those of native AC. This review focuses on the use of mechanical stimulation to attain and enhance the properties of AC constructs needed to translate these implants to the clinic. In-vivo, mechanical loading at maximal and supramaximal physiological levels has been shown to be detrimental to AC through the development of degenerative changes. In contrast, multiple studies have revealed that during culture, mechanical stimulation within narrow ranges of magnitude and duration can produce anisotropic, mechanically robust AC constructs with high cellular viability. Significant progress has been made in evaluating a variety of mechanical stimulation techniques on tissue-engineered AC, either alone or in combination with other stimuli. These advancements include determining and optimizing efficacious loading parameters (e.g., duration and frequency) to yield improvements in construct design criteria, such as collagen II content, compressive stiffness, cell viability, and fiber organization. With the advancement of mechanical stimulation as a potent strategy in AC tissue-engineering, a compendium detailing the results achievable by various stimulus regimens would be of great use for researchers in academia and industry. The objective is to list the qualitative and quantitative effects that can be attained when direct compression, hydrostatic pressure, shear

  7. A toolbox to explore the mechanics of living embryonic tissues

    OpenAIRE

    Camp?s, Otger

    2016-01-01

    The sculpting of embryonic tissues and organs into their functional morphologies involves the spatial and temporal regulation of mechanics at cell and tissue scales. Decades of in vitro work, complemented by some in vivo studies, have shown the relevance of mechanical cues in the control of cell behaviors that are central to developmental processes, but the lack of methodologies enabling precise, quantitative measurements of mechanical cues in vivo have hindered our understanding of the role ...

  8. Construction accidents: identification of the main associations between causes, mechanisms and stages of the construction process.

    Science.gov (United States)

    Carrillo-Castrillo, Jesús A; Trillo-Cabello, Antonio F; Rubio-Romero, Juan C

    2017-06-01

    To identify the most frequent causes of accidents in the construction sector in order to help safety practitioners in the task of prioritizing preventive actions depending on the stage of construction. Official accident investigation reports are analysed. A causation pattern is identified with the proportion of causes in each of the different possible groups of causes. Significant associations of the types of causes with accident mechanisms and construction stages have been identified. Significant differences have been found in accident causation depending on the mechanism of the accident and the construction stage ongoing. These results should be used to prioritize preventive actions to combat the most likely causes for each accident mechanism and construction stage.

  9. Clinically relevant mechanical testing of hernia graft constructs.

    Science.gov (United States)

    Sahoo, Sambit; DeLozier, Katherine R; Erdemir, Ahmet; Derwin, Kathleen A

    2015-01-01

    To understand the mechanical behavior of grafts in the context of hernia repair, there is a need to develop and adopt methods for mechanical testing of grafts in a clinically-relevant manner with clinically-relevant outcomes. Ball-burst and planar-biaxial methods were used to test three commercially-available hernia grafts (DermaMatrix, Biodesign, VitaMesh Blue). Both load-to-failure and cyclic fatigue tests were performed (n=6-11/group/test). Grafts were tested as sutured constructs in patch geometry. Dilatational strain analysis was performed considering the construct (both test methods) or the graft (planar-biaxial only) as the area of interest. DermaMatrix, Biodesign, and VitaMesh grafts showed differences in mechanical properties at the point of construct failure (load, in-plane load-per-suture and membrane tension) in ball-burst tests and differences in sub-failure properties (stiffness, dilatational strain at 16N/cm and cyclic mechanical properties) in planar-biaxial tests. In both load-to-failure and cyclic fatigue tests, each graft construct tended to be stiffer in planar-biaxial than ball-burst testing. In biaxial testing, the strain analysis method influenced the mechanical properties with the construct being more compliant than the graft. This study demonstrates that graft-fixation method, test mode and analysis method are important considerations for mechanical characterization of hernia grafts. Ball-burst tests can only estimate construct or material properties, whereas planar-biaxial tests capture anisotropy and can estimate construct, graft and material properties of the same test specimen. When the clinical performance of a graft in the context of hernia repair is of interest, testing a sutured construct and performing construct strain analysis arguably provides the most clinically-relevant assessment method. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Mechanical testing of hydrogels in cartilage tissue engineering: beyond the compressive modulus.

    Science.gov (United States)

    Xiao, Yinghua; Friis, Elizabeth A; Gehrke, Stevin H; Detamore, Michael S

    2013-10-01

    Injuries to articular cartilage result in significant pain to patients and high medical costs. Unfortunately, cartilage repair strategies have been notoriously unreliable and/or complex. Biomaterial-based tissue-engineering strategies offer great promise, including the use of hydrogels to regenerate articular cartilage. Mechanical integrity is arguably the most important functional outcome of engineered cartilage, although mechanical testing of hydrogel-based constructs to date has focused primarily on deformation rather than failure properties. In addition to deformation testing, as the field of cartilage tissue engineering matures, this community will benefit from the addition of mechanical failure testing to outcome analyses, given the crucial clinical importance of the success of engineered constructs. However, there is a tremendous disparity in the methods used to evaluate mechanical failure of hydrogels and articular cartilage. In an effort to bridge the gap in mechanical testing methods of articular cartilage and hydrogels in cartilage regeneration, this review classifies the different toughness measurements for each. The urgency for identifying the common ground between these two disparate fields is high, as mechanical failure is ready to stand alongside stiffness as a functional design requirement. In comparing toughness measurement methods between hydrogels and cartilage, we recommend that the best option for evaluating mechanical failure of hydrogel-based constructs for cartilage tissue engineering may be tensile testing based on the single edge notch test, in part because specimen preparation is more straightforward and a related American Society for Testing and Materials (ASTM) standard can be adopted in a fracture mechanics context.

  11. Vertex models: from cell mechanics to tissue morphogenesis.

    Science.gov (United States)

    Alt, Silvanus; Ganguly, Poulami; Salbreux, Guillaume

    2017-05-19

    Tissue morphogenesis requires the collective, coordinated motion and deformation of a large number of cells. Vertex model simulations for tissue mechanics have been developed to bridge the scales between force generation at the cellular level and tissue deformation and flows. We review here various formulations of vertex models that have been proposed for describing tissues in two and three dimensions. We discuss a generic formulation using a virtual work differential, and we review applications of vertex models to biological morphogenetic processes. We also highlight recent efforts to obtain continuum theories of tissue mechanics, which are effective, coarse-grained descriptions of vertex models.This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'. © 2017 The Authors.

  12. Mechanical appliances, mechanical movements and novelties of construction

    CERN Document Server

    Hiscox, Gardner D

    2008-01-01

    From the devices that power ships and trains to the workings of clocks, typewriters, and guns, this engrossing visual narrative profiles the specific and unique properties of hundreds of mechanical devices. Nearly 1,000 detailed illustrations depict steam-powered appliances, spring-powered devices, hydraulic equipment, and other machines, many of which remain in common use today. Each apparatus features a detailed line drawing and an informative explanation of its workings and uses. A final chapter chronicles 400 years of impassioned but futile searching for a perpetual motion machine.The comp

  13. Fibrous tissues growth and remodeling: Evolutionary micro-mechanical theory

    Science.gov (United States)

    Lanir, Yoram

    2017-10-01

    Living fibrous tissues are composite materials having the unique ability to adapt their size, shape, structure and mechanical properties in response to external loading. This adaptation, termed growth and remodeling (G&R), occurs throughout life and is achieved via cell-induced turnover of tissue constituents where some are degraded and new ones are produced. Realistic mathematical modeling of G&R provides insight into the basic processes, allows for hypotheses testing, and constitutes an essential tool for establishing clinical thresholds of pathological remodeling and for the production of tissue substitutes aimed to achieve target structure and properties. In this study, a general 3D micro-mechanical multi-scale theory of G&R in fibrous tissue was developed which connects between the evolution of the tissue structure and properties, and the underlying mechano-biological turnover events of its constituents. This structural approach circumvents a fundamental obstacle in modeling growth mechanics since the growth motion is not bijective. The model was realized for a flat tissue under two biaxial external loadings using data-based parameter values. The predictions show close similarity to characteristics of remodeled adult tissue including its structure, anisotropic and non-linear mechanical properties, and the onset of in situ pre-strain and pre-stress. The results suggest that these important features of living fibrous tissues evolve as they grow.

  14. Combination of biochemical and mechanical cues for tendon tissue engineering.

    Science.gov (United States)

    Testa, Stefano; Costantini, Marco; Fornetti, Ersilia; Bernardini, Sergio; Trombetta, Marcella; Seliktar, Dror; Cannata, Stefano; Rainer, Alberto; Gargioli, Cesare

    2017-11-01

    Tendinopathies negatively affect the life quality of millions of people in occupational and athletic settings, as well as the general population. Tendon healing is a slow process, often with insufficient results to restore complete endurance and functionality of the tissue. Tissue engineering, using tendon progenitors, artificial matrices and bioreactors for mechanical stimulation, could be an important approach for treating rips, fraying and tissue rupture. In our work, C3H10T1/2 murine fibroblast cell line was exposed to a combination of stimuli: a biochemical stimulus provided by Transforming Growth Factor Beta (TGF-β) and Ascorbic Acid (AA); a three-dimensional environment represented by PEGylated-Fibrinogen (PEG-Fibrinogen) biomimetic matrix; and a mechanical induction exploiting a custom bioreactor applying uniaxial stretching. In vitro analyses by immunofluorescence and mechanical testing revealed that the proposed combined approach favours the organization of a three-dimensional tissue-like structure promoting a remarkable arrangement of the cells and the neo-extracellular matrix, reflecting into enhanced mechanical strength. The proposed method represents a novel approach for tendon tissue engineering, demonstrating how the combined effect of biochemical and mechanical stimuli ameliorates biological and mechanical properties of the artificial tissue compared to those obtained with single inducement. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  15. Emerging Biofabrication Strategies for Engineering Complex Tissue Constructs

    DEFF Research Database (Denmark)

    Pedde, R. Daniel; Mirani, Bahram; Navaei, Ali

    2017-01-01

    The demand for organ transplantation and repair, coupled with a shortage of available donors, poses an urgent clinical need for the development of innovative treatment strategies for long-term repair and regeneration of injured or diseased tissues and organs. Bioengineering organs, by growing pat...

  16. Emerging Biofabrication Strategies for Engineering Complex Tissue Constructs.

    Science.gov (United States)

    Pedde, R Daniel; Mirani, Bahram; Navaei, Ali; Styan, Tara; Wong, Sarah; Mehrali, Mehdi; Thakur, Ashish; Mohtaram, Nima Khadem; Bayati, Armin; Dolatshahi-Pirouz, Alireza; Nikkhah, Mehdi; Willerth, Stephanie M; Akbari, Mohsen

    2017-05-01

    The demand for organ transplantation and repair, coupled with a shortage of available donors, poses an urgent clinical need for the development of innovative treatment strategies for long-term repair and regeneration of injured or diseased tissues and organs. Bioengineering organs, by growing patient-derived cells in biomaterial scaffolds in the presence of pertinent physicochemical signals, provides a promising solution to meet this demand. However, recapitulating the structural and cytoarchitectural complexities of native tissues in vitro remains a significant challenge to be addressed. Through tremendous efforts over the past decade, several innovative biofabrication strategies have been developed to overcome these challenges. This review highlights recent work on emerging three-dimensional bioprinting and textile techniques, compares the advantages and shortcomings of these approaches, outlines the use of common biomaterials and advanced hybrid scaffolds, and describes several design considerations including the structural, physical, biological, and economical parameters that are crucial for the fabrication of functional, complex, engineered tissues. Finally, the applications of these biofabrication strategies in neural, skin, connective, and muscle tissue engineering are explored. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering.

    Science.gov (United States)

    Carlier, Aurélie; Skvortsov, Gözde Akdeniz; Hafezi, Forough; Ferraris, Eleonora; Patterson, Jennifer; Koç, Bahattin; Van Oosterwyck, Hans

    2016-05-17

    Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.

  18. Low oxygen concentrations impair tissue development in tissue-engineered cardiovascular constructs

    NARCIS (Netherlands)

    Vlimmeren, M.A.A. van; Driessen-Mol, A.; Oomens, C.W.J.; Broek, M. van den; Stoop, R.; Bouten, C.V.C.; Baaijens, F.P.T.

    2012-01-01

    Cardiovascular tissue engineering has shown considerable progress, but in vitro tissue conditioning to stimulate the development of a functional extracellular matrix still needs improvement. We investigated the environmental factor oxygen concentration for its potential to increase the amount of

  19. Natural Rubber Nanocomposite with Human-Tissue-Like Mechanical Characteristic

    Science.gov (United States)

    Murniati, Riri; Novita, Nanda; Sutisna; Wibowo, Edy; Iskandar, Ferry; Abdullah, Mikrajuddin

    2017-07-01

    The blends of synthetic rubber and natural rubber with nanosilica were prepared using a blending technique in presence of different filler volume fraction. The effect of filler on morphological and mechanical characteristics was studied. Utilization of human cadaver in means of medical study has been commonly used primarily as tools of medical teaching and training such as surgery. Nonetheless, human cadaver brought inevitable problems. So it is necessary to find a substitute material that can be used to replace cadavers. In orthopaedics, the materials that resemble in mechanical properties to biological tissues are elastomers such as natural rubber (latex) and synthetic rubber (polyurethanes, silicones). This substitution material needs to consider the potential of Indonesia to help the development of the nation. Indonesia is the second largest country producer of natural rubber in the world. This paper aims to contribute to adjusting the mechanical properties of tissue-mimicking materials (TMMs) to the recommended range of biological tissue value and thus allow the development of phantoms with greater stability and similarity to human tissues. Repeatability for the phantom fabrication process was also explored. Characteristics were then compared to the control and mechanical characteristics of different human body part tissue. Nanosilica is the best filler to produce the best nanocomposite similarities with human tissue. We produced composites that approaching the properties of human internal tissues.

  20. Three-Dimensional Characterization of Tissue-Engineered Constructs by Contrast-Enhanced Nanofocus Computed Tomography

    OpenAIRE

    Papantoniou, Ioannis; Sonnaert, Maarten; Geris, Liesbet; Luyten, Frank P.; Schrooten, Jan; Kerckhofs, Greet

    2014-01-01

    To successfully implement tissue-engineered (TE) constructs as part of a clinical therapy, it is necessary to develop quality control tools that will ensure accurate and consistent TE construct release specifications. Hence, advanced methods to monitor TE construct properties need to be further developed. In this study, we showed proof of concept for contrast-enhanced nanofocus computed tomography (CE-nano-CT) as a whole-construct imaging technique with a noninvasive potential that enables th...

  1. Mechanical Strain Using 2D and 3D Bioreactors Induces Osteogenesis: Implications for Bone Tissue Engineering

    Science.gov (United States)

    van Griensven, M.; Diederichs, S.; Roeker, S.; Boehm, S.; Peterbauer, A.; Wolbank, S.; Riechers, D.; Stahl, F.; Kasper, C.

    Fracture healing is a complicated process involving many growth factors, cells, and physical forces. In cases, where natural healing is not able, efforts have to be undertaken to improve healing. For this purpose, tissue engineering may be an option. In order to stimulate cells to form a bone tissue several factors are needed: cells, scaffold, and growth factors. Stem cells derived from bone marrow or adipose tissues are the most useful in this regard. The differentiation of the cells can be accelerated using mechanical stimulation. The first part of this chapter describes the influence of longitudinal strain application. The second part uses a sophisticated approach with stem cells on a newly developed biomaterial (Sponceram) in a rotating bed bioreactor with the administration of bone morphogenetic protein-2. It is shown that such an approach is able to produce bone tissue constructs. This may lead to production of larger constructs that can be used in clinical applications.

  2. Dual-Scale Polymeric Constructs as Scaffolds for Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Federica Chiellini

    2011-03-01

    Full Text Available This research activity was aimed at the development of dual-scale scaffolds consisting of three-dimensional constructs of aligned poly(ε-caprolactone (PCL microfilaments and electrospun poly(lactic-co-glycolic acid (PLGA fibers. PCL constructs composed by layers of parallel microsized filaments (0/90° lay-down pattern, with a diameter of around 365 μm and interfilament distance of around 191 μm, were produced using a melt extrusion-based additive manufacturing technique. PLGA electrospun fibers with a diameter of around 1 μm were collected on top of the PCL constructs with different thicknesses, showing a certain degree of alignment. Cell culture experiments employing the MC3T3 murine preosteoblast cell line showed good cell viability and adhesion on the dual-scale scaffolds. In particular, the influence of electrospun fibers on cell morphology and behavior was evident, as well as in creating a structural bridging for cell colonization in the interfilament gap.

  3. The mechanics of development: Models and methods for tissue morphogenesis.

    Science.gov (United States)

    Gjorevski, Nikolce; Nelson, Celeste M

    2010-09-01

    Embryonic development is a physical process during which groups of cells are sculpted into functional organs. The mechanical properties of tissues and the forces exerted on them serve as epigenetic regulators of morphogenesis. Understanding these mechanobiological effects in the embryo requires new experimental approaches. Here we focus on branching of the lung airways and bending of the heart tube to describe examples of mechanical and physical cues that guide cell fate decisions and organogenesis. We highlight recent technological advances to measure tissue elasticity and endogenous mechanical stresses in real time during organ development. We also discuss recent progress in manipulating forces in intact embryos. © 2010 Wiley-Liss, Inc.

  4. The Influence of Bioreactor Geometry and the Mechanical Environment on Engineered Tissues

    KAUST Repository

    Osborne, J. M.

    2010-01-01

    A three phase model for the growth of a tissue construct within a perfusion bioreactor is examined. The cell population (and attendant extracellular matrix), culture medium, and porous scaffold are treated as distinct phases. The bioreactor system is represented by a two-dimensional channel containing a cell-seeded rigid porous scaffold (tissue construct), which is perfused with a culture medium. Through the prescription of appropriate functional forms for cell proliferation and extracellular matrix deposition rates, the model is used to compare the influence of cell density-, pressure-, and culture medium shear stress-regulated growth on the composition of the engineered tissue. The governing equations are derived in O\\'Dea et al. "A Three Phase Model for Tissue Construct Growth in a Perfusion Bioreactor," Math. Med. Biol., in which the long-wavelength limit was exploited to aid analysis; here, finite element methods are used to construct two-dimensional solutions to the governing equations and to investigate thoroughly their behavior. Comparison of the total tissue yield and averaged pressures, velocities, and shear stress demonstrates that quantitative agreement between the two-dimensional and long-wavelength approximation solutions is obtained for channel aspect ratios of order 10 -2 and that much of the qualitative behavior of the model is captured in the long-wavelength limit, even for relatively large channel aspect ratios. However, we demonstrate that in order to capture accurately the effect of mechanotransduction mechanisms on tissue construct growth, spatial effects in at least two dimensions must be included due to the inherent spatial variation of mechanical stimuli relevant to perfusion bioreactors, most notably, fluid shear stress, a feature not captured in the long-wavelength limit. Copyright © 2010 by ASME.

  5. Probing microscopic mechanical properties of hard tissues with Brillouin spectroscopy

    Science.gov (United States)

    Meng, Zhaokai; Yakovlev, Vladislav V.

    2015-02-01

    Mechanical properties of hard tissues play an important role in understanding underlying biological structures, as well as assessing the quality of artificial bone replacement materials. In this study, we employed Brillouin spectroscopy as a non-invasive approach to probe the microscopic elasticity of hard tissues, such as bones. Brillouin spectra were collected using a background free virtually imaged phased array spectrometer. As a reference, Raman spectra were also acquired for each imaging point. Experimental results reveal a positive correlation between the local concentration of the mineral content and the corresponding tissue stiffness, assessed through a Brillouin shift.

  6. Modulation of cell differentiation in bone tissue engineering constructs cultured in a bioreactor.

    NARCIS (Netherlands)

    Holtorf, H.L.; Jansen, J.A.; Mikos, A.G.

    2006-01-01

    In summary, many factors can influence the osteoblastic differentiation of marrow stromal cells when cultivated on three-dimensional tissue engineering scaffolds. In creating ideal bone tissue engineering constructs consisting of a combination of a scaffold, cells, and bioactive factors; a flow

  7. Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers.

    NARCIS (Netherlands)

    Levato, Riccardo; Visser, Jetze; Planell, Josep a; Engel, Elisabeth; Malda, Jos; Mateos-Timoneda, Miguel a

    2014-01-01

    Bioprinting allows the fabrication of living constructs with custom-made architectures by spatially controlled deposition of multiple bioinks. This is important for the generation of tissue, such as osteochondral tissue, which displays a zonal composition in the cartilage domain supported by the

  8. Antibiotic-Releasing Porous Polymethylmethacrylate/Gelatin/Antibiotic Constructs for Craniofacial Tissue Engineering

    Science.gov (United States)

    Shi, Meng; Kretlow, James D.; Spicer, Patrick P.; Tabata, Yasuhiko; Demian, Nagi; Wong, Mark E.; Kasper, F. Kurtis; Mikos, Antonios G.

    2011-01-01

    An antibiotic-releasing porous polymethylmethacrylate (PMMA) construct was developed to maintain the bony space and prime the wound site in the initial step of a two-stage regenerative medicine approach toward reconstructing significant bony or composite craniofacial tissue defects. Porous polymethylmethacrylate (PMMA) constructs incorporating gelatin microparticles (GMPs) were fabricated by the sequential assembly of GMPs, the antibiotic colistin, and a clinically used bone cement formulation of PMMA powder and methylmethacrylate liquid. PMMA/gelatin/antibiotic constructs with varying gelatin incorporation and drug content were investigated to elucidate the relationship between material composition and construct properties (porosity and drug release kinetics). The porosity of PMMA/gelatin/antibiotic constructs ranged between 7.6±1.8–38.4±1.4% depending on the amount of gelatin incorporated and the drug solution added for gelatin swelling. The constructs released colistin over 10 or 14 days with an average release rate per day above 10 µg/ml. The porosity and in vitro colistin release kinetics of PMMA/gelatin/antibiotic constructs were tuned by varying the material composition and fabrication parameters. This study demonstrates the potential of gelatin-incorporating PMMA constructs as a functional space maintainer for both promoting tissue healing/coverage and addressing local infections, enabling better long-term success of the definitive regenerated tissue construct. PMID:21295086

  9. Modeling the impact of scaffold architecture and mechanical loading on collagen turnover in engineered cardiovascular tissues.

    Science.gov (United States)

    Argento, G; de Jonge, N; Söntjens, S H M; Oomens, C W J; Bouten, C V C; Baaijens, F P T

    2015-06-01

    The anisotropic collagen architecture of an engineered cardiovascular tissue has a major impact on its in vivo mechanical performance. This evolving collagen architecture is determined by initial scaffold microstructure and mechanical loading. Here, we developed and validated a theoretical and computational microscale model to quantitatively understand the interplay between scaffold architecture and mechanical loading on collagen synthesis and degradation. Using input from experimental studies, we hypothesize that both the microstructure of the scaffold and the loading conditions influence collagen turnover. The evaluation of the mechanical and topological properties of in vitro engineered constructs reveals that the formation of extracellular matrix layers on top of the scaffold surface influences the mechanical anisotropy on the construct. Results show that the microscale model can successfully capture the collagen arrangement between the fibers of an electrospun scaffold under static and cyclic loading conditions. Contact guidance by the scaffold, and not applied load, dominates the collagen architecture. Therefore, when the collagen grows inside the pores of the scaffold, pronounced scaffold anisotropy guarantees the development of a construct that mimics the mechanical anisotropy of the native cardiovascular tissue.

  10. Glial Tissue Mechanics and Mechanosensing by Glial Cells

    Directory of Open Access Journals (Sweden)

    Katarzyna Pogoda

    2018-02-01

    Full Text Available Understanding the mechanical behavior of human brain is critical to interpret the role of physical stimuli in both normal and pathological processes that occur in CNS tissue, such as development, inflammation, neurodegeneration, aging, and most common brain tumors. Despite clear evidence that mechanical cues influence both normal and transformed brain tissue activity as well as normal and transformed brain cell behavior, little is known about the links between mechanical signals and their biochemical and medical consequences. A multi-level approach from whole organ rheology to single cell mechanics is needed to understand the physical aspects of human brain function and its pathologies. This review summarizes the latest achievements in the field.

  11. Tissue engineered esophagus scaffold constructed with porcine small intestinal submucosa and synthetic polymers.

    Science.gov (United States)

    Fan, Mei-Rong; Gong, Mei; Da, Lin-Cui; Bai, Lin; Li, Xiu-Qun; Chen, Ke-Fei; Li-Ling, Jesse; Yang, Zhi-Ming; Xie, Hui-Qi

    2014-02-01

    Acellular porcine small intestinal submucosa (SIS) has been successfully used for reconstructing esophagus with half circumferential defects. However, repairing full circumferential esophageal defects with SIS has been restricted due to the latter's poor mechanical properties. In the present study, synthetic polyesters biomaterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and poly(lactide-co-glycolide) (PLGA) have been used to improve the mechanical properties of SIS. Feasibility of SIS/PHBHHx-PLGA composite material scaffold for esophageal tissue engineering has been assessed through a series of testing. The appropriate mixing ratio of PHBHHx and PLGA polymers has been determined as 5:5 by mechanical testing and in vitro degradation experiment. The morphology of constructed membranous and tubular scaffolds was also characterized. As confirmed by enzyme-linked immunosorbent assay, the contents of VEGF and TGF-β have respectively reached 657 ± 18 ng mL(-1) and 130 ± 4 pg mL(-1) within the SIS/PHBHHx-PLGA specimens. Biocompatibility of the SIS/PHBHHx-PLGA specimens with rat bone marrow mesenchymal stem cells (MSCs) was also evaluated by scanning electron microscopy and a live-dead cell viability assay. Actin filaments of MSCs on the composite materials were labeled. Biological safety of the extract from SIS/PHBHHx-PLGA specimens, measured as hemolysis rate, was all lower than 5%. Compared with SIS and SIS/PHBHHx-PLGA specimens, inflammatory reaction provoked by the PHBHHx-PLGA specimens in rats was however more severe. Our results have suggested that SIS/PHBHHx-PLGA composite material can offer a new approach for esophageal tissue engineering.

  12. Construction of tissue-engineered small-diameter vascular grafts in fibrin scaffolds in 30 days.

    Science.gov (United States)

    Gui, Liqiong; Boyle, Michael J; Kamin, Yishai M; Huang, Angela H; Starcher, Barry C; Miller, Cheryl A; Vishnevetsky, Michael J; Niklason, Laura E

    2014-05-01

    Tissue-engineered small-diameter vascular grafts have been developed as a promising alternative to native veins or arteries for replacement therapy. However, there is still a crucial need to improve the current approaches to render the tissue-engineered blood vessels more favorable for clinical applications. A completely biological blood vessel (3-mm inner diameter) was constructed by culturing a 50:50 mixture of bovine smooth muscle cells (SMCs) with neonatal human dermal fibroblasts in fibrin gels. After 30 days of culture under pulsatile stretching, the engineered blood vessels demonstrated an average burst pressure of 913.3±150.1 mmHg (n=6), a suture retention (53.3±15.4 g) that is suitable for implantation, and a compliance (3.1%±2.5% per 100 mmHg) that is comparable to native vessels. These engineered grafts contained circumferentially aligned collagen fibers, microfibrils and elastic fibers, and differentiated SMCs, mimicking a native artery. These promising mechanical and biochemical properties were achieved in a very short culture time of 30 days, suggesting the potential of co-culturing SMCs with fibroblasts in fibrin gels to generate functional small-diameter vascular grafts for vascular reconstruction surgery.

  13. Construction of tissue microarrays using pre-existing slides as source of tissue when paraffin blocks are unavailable.

    Science.gov (United States)

    Deng, Fang-Ming; Zhao, Yan; Kong, Xiantian; Lee, Peng; Melamed, Jonathan

    2013-07-01

    To develop and validate a technique for construction of intermediate density tissue microarray (TMA) slides based on the transfer of tissue from pre-existing routine slides provided for pathology diagnosis with validation to show preservation of morphology and antigenicity of the transferred tissue. Prostate cancer patch TMAs were constructed using 20 cores acquired from radical prostatectomy histology slides. The preservation of morphology and antigenicity of these patch TMAs were tested with immunohistochemistry (IHC) in comparison to a traditional TMA. After IHC staining, 35 of 39 cores (89.7%) on the patch TMA were intact compared with 39 of 40 cores (97.5%) on the traditional TMA. Expression patterns and density of the antigens (34BE12, p63 and AMACR) on the patch TMA were almost identical to the traditional TMA. Patch TMA represents a viable alternative for tissue-based IHC studies when paraffin blocks are unavailable. This may be a valuable tool for allowing use of archival slide material for IHC and enable a standardized TMA platform to be used when the slides sent for review from other institutions are the only source of tissue available.

  14. A Lindenmayer system-based approach for the design of nutrient delivery networks in tissue constructs

    International Nuclear Information System (INIS)

    Yasar, Ozlem; Starly, Binil; Lan, S-F

    2009-01-01

    Large thick tissue constructs have reported limited success primarily due to the inability of cells to survive deep within the scaffold. Without access to adequate nutrients, cells placed deep within the tissue construct will die out, leading to non-uniform tissue regeneration. Currently, there is a necessity to design nutrient conduit networks within the tissue construct to enable cells to survive in the matrix. However, the design of complex networks within a tissue construct is challenging. In this paper, we present the Lindenmayer system, an elegant fractal-based language algorithm framework, to generate conduit networks in two- and three-dimensional architecture with several degrees of complexity. The conduit network maintains a parent-child relationship between each branch of the network. Several L-system parameters have been studied-branching angle, branch length, ratio of parent to child branch diameter, etc-to simulate several architectures under a given L-system notation. We have also presented a layered manufacturing-based UV-photopolymerization process using the Texas Instruments DLP(TM) system to fabricate the branched structures. This preliminary work showcases the applicability of L-system-based construct designs to drive scaffold fabrication systems.

  15. Engineering on the straight and narrow: the mechanics of nanofibrous assemblies for fiber-reinforced tissue regeneration.

    Science.gov (United States)

    Mauck, Robert L; Baker, Brendon M; Nerurkar, Nandan L; Burdick, Jason A; Li, Wan-Ju; Tuan, Rocky S; Elliott, Dawn M

    2009-06-01

    Tissue engineering of fibrous tissues of the musculoskeletal system represents a considerable challenge because of the complex architecture and mechanical properties of the component structures. Natural healing processes in these dense tissues are limited as a result of the mechanically challenging environment of the damaged tissue and the hypocellularity and avascular nature of the extracellular matrix. When healing does occur, the ordered structure of the native tissue is replaced with a disorganized fibrous scar with inferior mechanical properties, engendering sites that are prone to re-injury. To address the engineering of such tissues, we and others have adopted a structurally motivated approach based on organized nanofibrous assemblies. These scaffolds are composed of ultrafine polymeric fibers that can be fabricated in such a way to recreate the structural anisotropy typical of fiber-reinforced tissues. This straight-and-narrow topography not only provides tailored mechanical properties, but also serves as a 3D biomimetic micropattern for directed tissue formation. This review describes the underlying technology of nanofiber production and focuses specifically on the mechanical evaluation and theoretical modeling of these structures as it relates to native tissue structure and function. Applying the same mechanical framework for understanding native and engineered fiber-reinforced tissues provides a functional method for evaluating the utility and maturation of these unique engineered constructs. We further describe several case examples where these principles have been put to test, and discuss the remaining challenges and opportunities in forwarding this technology toward clinical implementation.

  16. Engineering on the Straight and Narrow: The Mechanics of Nanofibrous Assemblies for Fiber-Reinforced Tissue Regeneration

    Science.gov (United States)

    Baker, Brendon M.; Nerurkar, Nandan L.; Burdick, Jason A.; Li, Wan-Ju; Tuan, Rocky S.; Elliott, Dawn M.

    2009-01-01

    Tissue engineering of fibrous tissues of the musculoskeletal system represents a considerable challenge because of the complex architecture and mechanical properties of the component structures. Natural healing processes in these dense tissues are limited as a result of the mechanically challenging environment of the damaged tissue and the hypocellularity and avascular nature of the extracellular matrix. When healing does occur, the ordered structure of the native tissue is replaced with a disorganized fibrous scar with inferior mechanical properties, engendering sites that are prone to re-injury. To address the engineering of such tissues, we and others have adopted a structurally motivated approach based on organized nanofibrous assemblies. These scaffolds are composed of ultrafine polymeric fibers that can be fabricated in such a way to recreate the structural anisotropy typical of fiber-reinforced tissues. This straight-and-narrow topography not only provides tailored mechanical properties, but also serves as a 3D biomimetic micropattern for directed tissue formation. This review describes the underlying technology of nanofiber production and focuses specifically on the mechanical evaluation and theoretical modeling of these structures as it relates to native tissue structure and function. Applying the same mechanical framework for understanding native and engineered fiber-reinforced tissues provides a functional method for evaluating the utility and maturation of these unique engineered constructs. We further describe several case examples where these principles have been put to test, and discuss the remaining challenges and opportunities in forwarding this technology toward clinical implementation. PMID:19207040

  17. Tissue Acoustoelectric Effect Modeling From Solid Mechanics Theory.

    Science.gov (United States)

    Song, Xizi; Qin, Yexian; Xu, Yanbin; Ingram, Pier; Witte, Russell S; Dong, Feng

    2017-10-01

    The acoustoelectric (AE) effect is a basic physical phenomenon, which underlies the changes made in the conductivity of a medium by the application of focused ultrasound. Recently, based on the AE effect, several biomedical imaging techniques have been widely studied, such as ultrasound-modulated electrical impedance tomography and ultrasound current source density imaging. To further investigate the mechanism of the AE effect in tissue and to provide guidance for such techniques, we have modeled the tissue AE effect using the theory of solid mechanics. Both bulk compression and thermal expansion of tissue are considered and discussed. Computation simulation shows that the muscle AE effect result, conductivity change rate, is 3.26×10 -3 with 4.3-MPa peak pressure, satisfying the theoretical value. Bulk compression plays the main role for muscle AE effect, while thermal expansion makes almost no contribution to it. In addition, the AE signals of porcine muscle are measured at different focal positions. With the same magnitude order and the same change trend, the experiment result confirms that the simulation result is effective. Both simulation and experimental results validate that tissue AE effect modeling using solid mechanics theory is feasible, which is of significance for the further development of related biomedical imaging techniques.

  18. Fluid mechanics as a driver of tissue-scale mechanical signaling in organogenesis.

    Science.gov (United States)

    Gilbert, Rachel M; Morgan, Joshua T; Marcin, Elizabeth S; Gleghorn, Jason P

    2016-12-01

    Organogenesis is the process during development by which cells self-assemble into complex, multi-scale tissues. Whereas significant focus and research effort has demonstrated the importance of solid mechanics in organogenesis, less attention has been given to the fluid forces that provide mechanical cues over tissue length scales. Fluid motion and pressure is capable of creating spatial gradients of forces acting on cells, thus eliciting distinct and localized signaling patterns essential for proper organ formation. Understanding the multi-scale nature of the mechanics is critically important to decipher how mechanical signals sculpt developing organs. This review outlines various mechanisms by which tissues generate, regulate, and sense fluid forces and highlights the impact of these forces and mechanisms in case studies of normal and pathological development.

  19. Mechanized syringe homogenization of human and animal tissues.

    Science.gov (United States)

    Kurien, Biji T; Porter, Andrew C; Patel, Nisha C; Kurono, Sadamu; Matsumoto, Hiroyuki; Scofield, R Hal

    2004-06-01

    Tissue homogenization is a prerequisite to any fractionation schedule. A plethora of hands-on methods are available to homogenize tissues. Here we report a mechanized method for homogenizing animal and human tissues rapidly and easily. The Bio-Mixer 1200 (manufactured by Innovative Products, Inc., Oklahoma City, OK) utilizes the back-and-forth movement of two motor-driven disposable syringes, connected to each other through a three-way stopcock, to homogenize animal or human tissue. Using this method, we were able to homogenize human or mouse tissues (brain, liver, heart, and salivary glands) in 5 min. From sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and a matrix-assisted laser desorption/ionization time-of-flight mass spectrometric enzyme assay for prolidase, we have found that the homogenates obtained were as good or even better than that obtained used a manual glass-on-Teflon (DuPont, Wilmington, DE) homogenization protocol (all-glass tube and Teflon pestle). Use of the Bio-Mixer 1200 to homogenize animal or human tissue precludes the need to stay in the cold room as is the case with the other hands-on homogenization methods available, in addition to freeing up time for other experiments.

  20. Ultrasound Imaging Techniques for Spatiotemporal Characterization of Composition, Microstructure, and Mechanical Properties in Tissue Engineering.

    Science.gov (United States)

    Deng, Cheri X; Hong, Xiaowei; Stegemann, Jan P

    2016-08-01

    Ultrasound techniques are increasingly being used to quantitatively characterize both native and engineered tissues. This review provides an overview and selected examples of the main techniques used in these applications. Grayscale imaging has been used to characterize extracellular matrix deposition, and quantitative ultrasound imaging based on the integrated backscatter coefficient has been applied to estimating cell concentrations and matrix morphology in tissue engineering. Spectral analysis has been employed to characterize the concentration and spatial distribution of mineral particles in a construct, as well as to monitor mineral deposition by cells over time. Ultrasound techniques have also been used to measure the mechanical properties of native and engineered tissues. Conventional ultrasound elasticity imaging and acoustic radiation force imaging have been applied to detect regions of altered stiffness within tissues. Sonorheometry and monitoring of steady-state excitation and recovery have been used to characterize viscoelastic properties of tissue using a single transducer to both deform and image the sample. Dual-mode ultrasound elastography uses separate ultrasound transducers to produce a more potent deformation force to microscale characterization of viscoelasticity of hydrogel constructs. These ultrasound-based techniques have high potential to impact the field of tissue engineering as they are further developed and their range of applications expands.

  1. Sol gel-derived hydroxyapatite films over porous calcium polyphosphate substrates for improved tissue engineering of osteochondral-like constructs.

    Science.gov (United States)

    Lee, Whitaik David; Gawri, Rahul; Pilliar, Robert M; Stanford, William L; Kandel, Rita A

    2017-10-15

    Integration of in vitro-formed cartilage on a suitable substrate to form tissue-engineered implants for osteochondral defect repair is a considerable challenge. In healthy cartilage, a zone of calcified cartilage (ZCC) acts as an intermediary for mechanical force transfer from soft to hard tissue, as well as an effective interlocking structure to better resist interfacial shear forces. We have developed biphasic constructs that consist of scaffold-free cartilage tissue grown in vitro on, and interdigitated with, porous calcium polyphosphate (CPP) substrates. However, as CPP degrades, it releases inorganic polyphosphates (polyP) that can inhibit local mineralization, thereby preventing the formation of a ZCC at the interface. Thus, we hypothesize that coating CPP substrate with a layer of hydroxyapatite (HA) might prevent or limit this polyP release. To investigate this we tested both inorganic or organic sol-gel processing methods, asa barrier coating on CPP substrate to inhibit polyP release. Both types of coating supported the formation of ZCC in direct contact with the substrate, however the ZCC appeared more continuous in the tissue formed on the organic HA sol gel coated CPP. Tissues formed on coated substrates accumulated comparable quantities of extracellular matrix and mineral, but tissues formed on organic sol-gel (OSG)-coated substrates accumulated less polyP than tissues formed on inorganic sol-gel (ISG)-coated substrates. Constructs formed with OSG-coated CPP substrates had greater interfacial shear strength than those formed with ISG-coated and non-coated substrates. These results suggest that the OSG coating method can modify the location and distribution of ZCC and can be used to improve the mechanical integrity of tissue-engineered constructs formed on porous CPP substrates. Articular cartilage interfaces with bone through a zone of calcified cartilage. This study describes a method to generate an "osteochondral-like" implant that mimics this

  2. Dental pulp stem cells express tendon markers under mechanical loading and are a potential cell source for tissue engineering of tendon-like tissue.

    Science.gov (United States)

    Chen, Yu-Ying; He, Sheng-Teng; Yan, Fu-Hua; Zhou, Peng-Fei; Luo, Kai; Zhang, Yan-Ding; Xiao, Yin; Lin, Min-Kui

    2016-12-16

    Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells (DPSCs) for potential application in tendon tissue engineering. The expression of tendon-related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid (PGA) fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a potential stem cell source for tissue engineering of tendon-like tissue.

  3. Mechanical Stimulation of Adipose-Derived Stem Cells for Functional Tissue Engineering of the Musculoskeletal System via Cyclic Hydrostatic Pressure, Simulated Microgravity, and Cyclic Tensile Strain.

    Science.gov (United States)

    Nordberg, Rachel C; Bodle, Josie C; Loboa, Elizabeth G

    2018-01-01

    It is critical that human adipose stem cell (hASC) tissue-engineering therapies possess appropriate mechanical properties in order to restore function of the load bearing tissues of the musculoskeletal system. In an effort to elucidate the hASC response to mechanical stimulation and develop mechanically robust tissue engineered constructs, recent research has utilized a variety of mechanical loading paradigms including cyclic tensile strain, cyclic hydrostatic pressure, and mechanical unloading in simulated microgravity. This chapter describes methods for applying these mechanical stimuli to hASC to direct differentiation for functional tissue engineering of the musculoskeletal system.

  4. Practical considerations in the design and construction of tissue-equivalent proportional counters

    International Nuclear Information System (INIS)

    Braby, L.A.; Johnson, G.W.

    1995-01-01

    The design and construction techniques required to produce high quality tissue-equivalent proportional counters are not difficult, but there are a few special considerations. Since there are many options at each stage of the design and construction, and each choice may affect subsequent steps in the process, it is important to consider the entire process. Many successful techniques have been developed by the research groups that have constructed specialised detectors for the requirements of their research. These techniques can generally be extended to the construction of other detectors. Information on design, materials selection, and construction techniques which have proved to be useful in the construction of a wide variety of detectors is presented. (author)

  5. The construction and practice of GIS ontology service mechanism

    Science.gov (United States)

    Yang, Kun; Wang, Jun; Peng, Shuang-yun; Cheng, Hong-ping

    2005-10-01

    With the development of Semantic Web technology, the spatial information service based on ontology is an effective way for sharing and interoperation of heterogeneous information resources in the distributed network environment. Based on the deep analysis for the spatial information service mechanism of geo-ontology, the system construction strategy and service workflow and combined with the present mainstream commercial GIS software packages, three solutions of system construction for spatial information sharing and interoperation have been proposed here in this paper. The different geographic information application systems distributed on the internet may be integrated dynamically and openly by using one of the three solutions for realizing the sharing and interoperation of heterogeneous spatial information resources in the distributing environment. In order to realize the practical applications of spatial information sharing and interoperation in different brunches of police system, a prototype system for crime case information sharing based on geo-ontology has also been developed by using the methods described above.

  6. Constructing a Computer Model of the Human Eye Based on Tissue Slice Images

    OpenAIRE

    Dai, Peishan; Wang, Boliang; Bao, Chunbo; Ju, Ying

    2010-01-01

    Computer simulation of the biomechanical and biological heat transfer in ophthalmology greatly relies on having a reliable computer model of the human eye. This paper proposes a novel method on the construction of a geometric model of the human eye based on tissue slice images. Slice images were obtained from an in vitro Chinese human eye through an embryo specimen processing methods. A level set algorithm was used to extract contour points of eye tissues while a principle component analysi...

  7. Fundamental Mechanisms of Pulsed Laser Ablation of Biological Tissue

    Science.gov (United States)

    Albagli, Douglas

    The ability to cut and remove biological tissue with short pulsed laser light, a process called laser ablation, has the potential to revolutionize many surgical procedures. Ablation procedures using short pulsed lasers are currently being developed or used in many fields of medicine, including cardiology, ophthalmology, dermatology, dentistry, orthopedics, and urology. Despite this, the underlying physics of the ablation process is not well understood. In fact, there is wide disagreement over whether the fundamental mechanism is primarily photothermal, photomechanical, or photochemical. In this thesis, both experimental and theoretical techniques are developed to explore this issue. The photothermal model postulates that ablation proceeds through vaporization of the target material. The photomechanical model asserts that ablation is initiated when the laser-induced tensile stress exceeds the ultimate tensile strength of the target. I have developed a three dimensional model of the thermoelastic response of tissue to short pulsed laser irradiation which allows the time dependent stress distribution to be calculated given the optical, thermal and mechanical properties of the target. A complimentary experimental technique has been developed to verify this model, measure the needed physical properties of the tissue, and record the thermoelastic response of the tissue at the onset of ablation. The results of this work have been widely disseminated to the international research community and have led to significant findings which support the photomechanical model of ablation of tissue. First, the energy deposited in tissue is an order of magnitude less than that required for vaporization. Second, unlike the one-dimensional thermoelastic model of laser-induced stress generation that has appeared in the literature, the full three-dimensional model predicts the development of significant tensile stresses on the surface of the target, precisely where ablation is observed to

  8. The design and construction of an electrohydrodynamic cartesian robot for the preparation of tissue engineering constructs.

    Directory of Open Access Journals (Sweden)

    Shaikh Hafeez Hashimdeen

    Full Text Available In this work we bring together replicating rapid prototyping technology with electrohydrodynamic phenomena to develop a device with the ability to build structures in three-dimensions while simultaneously affording the user a degree of designing versatility and ease that is not seen in conventional computer numerically controlled machines. An attempt at reproducing an actual human ear using polycaprolactone was pursued to validate the hardware. Five different polycaprolactone solution concentrations between 7-15 wt% were used and printing was performed at applied voltages that ranged from 1 to 6 kV and at flow rates from 5 µl/min to 60 µl/min. The corresponding geometrical and aesthetic features of the printed constructs were studied to determine the effectiveness of the device. The 15 wt% concentration at 60 µl/min under an applied electric field of 6 kV was identified as the best operating parameters to work with.

  9. Tuning Cell and Tissue Development by Combining Multiple Mechanical Signals.

    Science.gov (United States)

    Sinha, Ravi; Verdonschot, Nico; Koopman, Bart; Rouwkema, Jeroen

    2017-10-01

    Mechanical signals offer a promising way to control cell and tissue development. It has been established that cells constantly probe their mechanical microenvironment and employ force feedback mechanisms to modify themselves and when possible, their environment, to reach a homeostatic state. Thus, a correct mechanical microenvironment (external forces and mechanical properties and shapes of cellular surroundings) is necessary for the proper functioning of cells. In vitro or in the case of nonbiological implants in vivo, where cells are in an artificial environment, addition of the adequate mechanical signals can, therefore, enable the cells to function normally as in vivo. Hence, a wide variety of approaches have been developed to apply mechanical stimuli (such as substrate stretch, flow-induced shear stress, substrate stiffness, topography, and modulation of attachment area) to cells in vitro. These approaches have not just revealed the effects of the mechanical signals on cells but also provided ways for probing cellular molecules and structures that can provide a mechanistic understanding of the effects. However, they remain lower in complexity compared with the in vivo conditions, where the cellular mechanical microenvironment is the result of a combination of multiple mechanical signals. Therefore, combinations of mechanical stimuli have also been applied to cells in vitro. These studies have had varying focus-developing novel platforms to apply complex combinations of mechanical stimuli, observing the co-operation/competition between stimuli, combining benefits of multiple stimuli toward an application, or uncovering the underlying mechanisms of their action. In general, they provided new insights that could not have been predicted from previous knowledge. We present here a review of several such studies and the insights gained from them, thereby making a case for such studies to be continued and further developed.

  10. Complex heterogeneous tissue constructs containing multiple cell types prepared by inkjet printing technology.

    Science.gov (United States)

    Xu, Tao; Zhao, Weixin; Zhu, Jian-Ming; Albanna, Mohammad Z; Yoo, James J; Atala, Anthony

    2013-01-01

    This study was designed to develop a versatile method for fabricating complex and heterogeneous three-dimensional (3D) tissue constructs using simultaneous ink-jetting of multiple cell types. Human amniotic fluid-derived stem cells (hAFSCs), canine smooth muscle cells (dSMCs), and bovine aortic endothelial cells (bECs), were separately mixed with ionic cross-linker calcium chloride (CaCl(2)), loaded into separate ink cartridges and printed using a modified thermal inkjet printer. The three cell types were delivered layer-by-layer to pre-determined locations in a sodium alginate-collagen composite located in a chamber under the printer. The reaction between CaCl(2) and sodium alginate resulted in a rapid formation of a solid composite gel and the printed cells were anchored in designated areas within the gel. The printing process was repeated for several cycles leading to a complex 3D multi-cell hybrid construct. The biological functions of the 3D printed constructs were evaluated in vitro and in vivo. Each of the printed cell types maintained their viability and normal proliferation rates, phenotypic expression, and physiological functions within the heterogeneous constructs. The bioprinted constructs were able to survive and mature into functional tissues with adequate vascularization in vivo. These findings demonstrate the feasibility of fabricating complex heterogeneous tissue constructs containing multiple cell types using inkjet printing technology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. In-vivo mechanical tissue property measurement for improved simulations

    Science.gov (United States)

    Ottensmeyer, Mark P.; Salisbury, J. Kenneth, Jr.

    2000-08-01

    Surgical training today, beyond what can be learned in didactic form or practice on animal or other models, is subject to the availability of appropriate training cases from which students can learn. This is especially true for battlefield surgery, as civilian hospitals may not expose doctors to frequent examples of relevant injuries. To provide a more uniform training experience, covering a standard suite of typical operations without relying on the misfortune of patients requiring surgery, many groups are developing computer-based surgical simulation systems. One of the current areas of development is the implementation of force and tactile (haptic) feedback in simulations. To create a model with realistic haptic feedback, knowledge of the material properties of the tissues in question is essential. While there is much data from tissue samples in vitro, the properties of living tissue in situ are mostly unknown. From the data that is available, it is clear that living tissue and tissue in vitro can have radically different mechanical properties. For this reason, our group is developing surgical tools that will be able to measure the force-displacement characteristics of a variety of tissues in living organisms. Taking these data over the range of frequencies relevant to haptic simulation provides information to extract stiffness and material damping parameters of different kinds of tissue. The tools are being designed for use during minimally invasive surgery, but will permit data to be acquired either during MIS or open procedures. Animal tests are expected to commence in early 2000, but the tools are being designed with safety considerations in mind for eventual use in humans. Data will be taken both for solid organs and for selected elements of the vasculature. These data will be used in simulation systems under development at the Center for Innovative Minimally Invasive Therapy at Massachusetts General Hospital and the Laboratory for Human and Machine Haptics

  12. Beta II plasma-gun mechanical design and construction

    International Nuclear Information System (INIS)

    Pedrotti, L.; Deis, G.; Wong, R.; Calderon, M.; Chargin, A.; Garner, D.

    1979-01-01

    The magnetized coaxial plasma gun (located on the east end of the Beta II facility at the Lawrence Livermore Laboratory) will be used to test a new method of initiating a field reversed mirror plasma. The field-reversed mirror is expected to improve the mirror-fusion reactor by enhancing the ratio of fusion power to injected power. This paper concentrates on the mechanical design and construction of the magnetized coaxial plasma gun and also discusses the diagnostic devices necessary to demonstrate the formation of field-reversed rings

  13. On construction of quantum mechanics on cubic forms

    International Nuclear Information System (INIS)

    Yamaleev, R.M.

    1989-01-01

    One of the ways is studied of constructing Quantum Mechanics on cubic forms with a wave function in the field of Greav's numbers. The corresponding cubic forms and transformations such as rotation which remain invariant these cubic forms are determined. The properties of geometric elements on cubic forms and Dicson algebra of the cubic degree are described. We give definitions of triunitary operator, creation operators for trilinear oscillator and operator of trispin. Analogs of the energy operator of Pauli equation and the relativistic relationship between energy, momentum and mass are considered. 10 refs

  14. Conservative diffusions: a constructive approach to Nelson's stochastic mechanics

    International Nuclear Information System (INIS)

    Carlen, E.A.

    1984-01-01

    In Nelson's stochastic mechanics, quantum phenomena are described in terms of diffusions instead of wave functions; this thesis is a study of that description. Concern here is with the possibility of describing, as opposed to explaining, quantum phenomena in terms of diffusions. In this direction, the following questions arise: ''Do the diffusion of stochastic mechanics - which are formally given by stochastic differential equations with extremely singular coefficients - really exist.'' Given that they exist, one can ask, ''Do these diffusions have physically reasonable paths to study the behavior of physical systems.'' These are the questions treated in this thesis. In Chapter 1, stochastic mechanics and diffusion theory are reviewed, using the Guerra-Morato variational principle to establish the connection with the Schroedinger equation. Chapter II settles the first of the questions raised above. Using PDE methods, the diffusions of stochastic mechanics are constructed. The result is sufficiently general to be of independent mathematical interest. In Chapter III, potential scattering in stochastic mechanics is treated and direct probabilistic methods of studying quantum scattering problems are discussed. The results provide a solid YES in answer to the second question raised above

  15. 3D Printing of Tissue Engineered Constructs for In Vitro Modeling of Disease Progression and Drug Screening.

    Science.gov (United States)

    Vanderburgh, Joseph; Sterling, Julie A; Guelcher, Scott A

    2017-01-01

    2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D vs. 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs.

  16. Multiaxial mechanical response and constitutive modeling of esophageal tissues: Impact on esophageal tissue engineering.

    Science.gov (United States)

    Sommer, Gerhard; Schriefl, Andreas; Zeindlinger, Georg; Katzensteiner, Andreas; Ainödhofer, Herwig; Saxena, Amulya; Holzapfel, Gerhard A

    2013-12-01

    Congenital defects of the esophagus are relatively frequent, with 1 out of 2500 babies suffering from such a defect. A new method of treatment by implanting tissue engineered esophagi into newborns is currently being developed and tested using ovine esophagi. For the reconstruction of the biological function of native tissues with engineered esophagi, their cellular structure as well as their mechanical properties must be considered. Since very limited mechanical and structural data for the esophagus are available, the aim of this study was to investigate the multiaxial mechanical behavior of the ovine esophagus and the underlying microstructure. Therefore, uniaxial tensile, biaxial tensile and extension-inflation tests on esophagi were performed. The underlying microstructure was examined in stained histological sections through standard optical microscopy techniques. Moreover, the uniaxial ultimate tensile strength and residual deformations of the tissue were determined. Both the mucosa-submucosa and the muscle layers showed nonlinear and anisotropic mechanical behavior during uniaxial, biaxial and inflation testing. Cyclical inflation of the intact esophageal tube caused marked softening of the passive esophagi in the circumferential direction. The rupture strength of the mucosa-submucosa layer was much higher than that of the muscle layer. Overall, the ovine esophagus showed a heterogeneous and anisotropic behavior with different mechanical properties for the individual layers. The intact and layer-specific multiaxial properties were characterized using a well-known three-dimensional microstructurally based strain-energy function. This novel and complete set of data serves the basis for a better understanding of tissue remodeling in diseased esophagi and can be used to perform computer simulations of surgical interventions or medical-device applications. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  17. Construction of three-dimensional vascularized cardiac tissue with cell sheet engineering.

    Science.gov (United States)

    Sakaguchi, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

    2015-05-10

    Construction of three-dimensional (3D) tissues with pre-isolated cells is a promising achievement for novel medicine and drug-discovery research. Our laboratory constructs 3D tissues with an innovative and unique method for layering multiple cell sheets. Cell sheets maintain a high-efficiently regenerating function, because of the higher cell density and higher transplantation efficiency, compared to other cell-delivery methods. Cell sheets have already been applied in clinical applications for regenerative medicine in treating patients with various diseases. Therefore, in our search to develop a more efficient treatment with cell sheets, we are constructing 3D tissues by layering cell sheets. Native animal tissues and organs have an abundance of capillaries to supply oxygen and nutrients, and to remove waste molecules. In our investigation of vascularized cardiac cell sheets, we have found that endothelial cells within cell sheets spontaneously form blood vessel networks as in vivo capillaries. To construct even thicker 3D tissues by layering multiple cell sheets, it is critical to have a medium or blood flow within the vascular networks of the cell sheets. Therefore, to perfuse medium or blood in the cell sheet vascular network to maintain the viability of all cells, we developed two types of vascular beds; (1) a femoral muscle-based vascular bed, and (2) a synthetic collagen gel-based vascular bed. Both vascular beds successfully provide the critical flow of culture medium, which allows 12-layer cell sheets to survive. Such bioreactor systems, when combined with cell sheet engineering techniques, have produced functional vascularized 3D tissues. Here we explain and discuss the various processes to obtain vascular networks by properly connecting cell sheets and the engineering of 3D tissues. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Design and construction of a planar motion mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Tanasovici, Gilberto [Protemaq Engenharia e Projetos, Santo Andre, SP (Brazil); Fucatu, Carlos H. [Technomar Engenharia Ltda., Sao Paulo, SP (Brazil); Tannuri, Eduardo A. [Universidade de Sao Paulo (USP), SP (Brazil). Escola Politecnica. Dept. de Engenharia Mecatronica; Umeda, Carlos H. [Instituto de Pesquisas Tecnologicas (IPT), Sao Paulo, SP (Brazil)

    2008-07-01

    This paper describes the design and construction of a PMM (Planar Motion Mechanism) towed by the IPT-SP main carriage. The IPT towing tank no. 2 is 220 m length and 6.6 m wide. The PMM provides a forced sway and/or yaw oscillation on a ship or other marine structure scaled model.. The maximum sway amplitude (transversal motion) is {+-}1 m, and the maximum sway velocity is 1.0 m/s, with a maximum carrying load of 1000 N. The maximum yaw velocity (rotation motion) is 36 deg/s. High-precision components were used in the construction, and the final estimated accuracy in the sway axis is 0.02 mm and approximately 0.1 deg for yaw motions. Finite Element Analysis and Structural Optimization techniques were used during the design stage. The PMM structure total mass is less than 1 ton, lighter than similar mechanisms in other institutions. A Man-Machine Interface was developed, and the operator is able to define the period and amplitude of sway and yaw motions, as well as the fade-in and fade-out time. An integral 3-component force load cell is installed in the end of the support axis, which measures the hydrodynamic loads on the captive model at low speed tests. This novel laboratorial facility allows the IPT to execute new kinds of experimental procedures, related to evaluation of hydrodynamic loads acting on ship hulls and offshore structures. (author)

  19. Smooth muscle-like tissue constructs with circumferentially oriented cells formed by the cell fiber technology.

    Directory of Open Access Journals (Sweden)

    Amy Y Hsiao

    Full Text Available The proper functioning of many organs and tissues containing smooth muscles greatly depends on the intricate organization of the smooth muscle cells oriented in appropriate directions. Consequently controlling the cellular orientation in three-dimensional (3D cellular constructs is an important issue in engineering tissues of smooth muscles. However, the ability to precisely control the cellular orientation at the microscale cannot be achieved by various commonly used 3D tissue engineering building blocks such as spheroids. This paper presents the formation of coiled spring-shaped 3D cellular constructs containing circumferentially oriented smooth muscle-like cells differentiated from dedifferentiated fat (DFAT cells. By using the cell fiber technology, DFAT cells suspended in a mixture of extracellular proteins possessing an optimized stiffness were encapsulated in the core region of alginate shell microfibers and uniformly aligned to the longitudinal direction. Upon differentiation induction to the smooth muscle lineage, DFAT cell fibers self-assembled to coiled spring structures where the cells became circumferentially oriented. By changing the initial core-shell microfiber diameter, we demonstrated that the spring pitch and diameter could be controlled. 21 days after differentiation induction, the cell fibers contained high percentages of ASMA-positive and calponin-positive cells. Our technology to create these smooth muscle-like spring constructs enabled precise control of cellular alignment and orientation in 3D. These constructs can further serve as tissue engineering building blocks for larger organs and cellular implants used in clinical treatments.

  20. Osteochondral tissue engineering for total joint repair critical steps towards cell based constructs

    NARCIS (Netherlands)

    Hamann, D.

    2008-01-01

    This thesis identifies critical steps to be taken to develop osteochondral constructs. One of the most significant steps in cell-based tissue engineering (TE) is efficient and effective cell seeding. The application of multipotent mesenchymal stem cells (MSCs) is a major advantage for bone and

  1. Smooth muscle-like tissue constructs with circumferentially oriented cells formed by the cell fiber technology.

    Science.gov (United States)

    Hsiao, Amy Y; Okitsu, Teru; Onoe, Hiroaki; Kiyosawa, Mahiro; Teramae, Hiroki; Iwanaga, Shintaroh; Kazama, Tomohiko; Matsumoto, Taro; Takeuchi, Shoji

    2015-01-01

    The proper functioning of many organs and tissues containing smooth muscles greatly depends on the intricate organization of the smooth muscle cells oriented in appropriate directions. Consequently controlling the cellular orientation in three-dimensional (3D) cellular constructs is an important issue in engineering tissues of smooth muscles. However, the ability to precisely control the cellular orientation at the microscale cannot be achieved by various commonly used 3D tissue engineering building blocks such as spheroids. This paper presents the formation of coiled spring-shaped 3D cellular constructs containing circumferentially oriented smooth muscle-like cells differentiated from dedifferentiated fat (DFAT) cells. By using the cell fiber technology, DFAT cells suspended in a mixture of extracellular proteins possessing an optimized stiffness were encapsulated in the core region of alginate shell microfibers and uniformly aligned to the longitudinal direction. Upon differentiation induction to the smooth muscle lineage, DFAT cell fibers self-assembled to coiled spring structures where the cells became circumferentially oriented. By changing the initial core-shell microfiber diameter, we demonstrated that the spring pitch and diameter could be controlled. 21 days after differentiation induction, the cell fibers contained high percentages of ASMA-positive and calponin-positive cells. Our technology to create these smooth muscle-like spring constructs enabled precise control of cellular alignment and orientation in 3D. These constructs can further serve as tissue engineering building blocks for larger organs and cellular implants used in clinical treatments.

  2. Post-operative re-construction of dentoalveolar tissue and the ...

    African Journals Online (AJOL)

    Post-operative re-construction of dentoalveolar tissue and the mandible and maxillae using prosthetic therapy. R Mutave, ML Chindia, SW Guthua. Abstract. Objective: To determine the range of ablative surgery and rehabilitative procedures performed on maxillofacial structures. Design: A retrospective descriptive study.

  3. Chondroprotective supplementation promotes the mechanical properties of injectable scaffold for human nucleus pulposus tissue engineering.

    Science.gov (United States)

    Foss, Berit L; Maxwell, Thomas W; Deng, Ying

    2014-01-01

    A result of intervertebral disc (IVD) degeneration, the nucleus pulposus (NP) is no longer able to withstand applied load leading to pain and disability. The objective of this study is to fabricate a tissue-engineered injectable scaffold with chondroprotective supplementation in vitro to improve the mechanical properties of a degenerative NP. Tissue-engineered scaffolds were fabricated using different concentrations of alginate and calcium chloride and mechanically evaluated. Fabrication conditions were based on structural and mechanical resemblance to the native NP. Chondroprotective supplementation, glucosamine (GCSN) and chondroitin sulfate (CS), were added to scaffolds at concentrations of 0:0µg/mL (0:0-S), 125:100µg/mL (125:100-S), 250:200µg/mL (250:200-S), and 500:400µg/mL (500:400-S), GCSN and CS, respectively. Scaffolds were used to fabricate tissue-engineered constructs through encapsulation of human nucleus pulposus cells (HNPCs). The tissue-engineered constructs were collected at days 1, 14, and 28 for biochemical and biomechanical evaluations. Confocal microscopy showed HNPC viability and rounded morphology over the 28 day period. MTT analysis resulted in significant increases in cell proliferation for each group. Collagen type II ELISA quantification and compressive aggregate moduli (HA) showed increasing trends for both 250:200-S and the 500:400-S groups on Day 28 with significantly greater HA compared to 0:0-S group. Glycosaminoglycan and water content decreased for all groups. Results indicate the increased mechanical properties of the 250:200-S and the 500:400-S was due to production of a functional matrix. This study demonstrated potential for a chondroprotective supplemented injectable scaffold to restore biomechanical function of a degenerative disc through the production of a mechanically functional matrix. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Tissue engineering of flexor tendons: the effect of a tissue bioreactor on adipoderived stem cell-seeded and fibroblast-seeded tendon constructs.

    Science.gov (United States)

    Angelidis, Ioannis K; Thorfinn, Johan; Connolly, Ian D; Lindsey, Derek; Pham, Hung M; Chang, James

    2010-09-01

    Tissue-engineered flexor tendons could eventually be used for reconstruction of large tendon defects. The goal of this project was to examine the effect of a tissue bioreactor on the biomechanical properties of tendon constructs seeded with adipoderived stem cells (ASCs) and fibroblasts (Fs). Rabbit rear paw flexor tendons were acellularized and seeded with ASCs or Fs. A custom bioreactor applied a cyclic mechanical load of 1.25 N at 1 cycle/minute for 5 days onto the tendon constructs. Three additional groups were used as controls: fresh tendons and tendons reseeded with either ASCs or Fs that were not exposed to the bioreactor treatment and were left in stationary incubation for 5 days. We compared the ultimate tensile stress (UTS) and elastic modulus (EM) of bioreactor-treated tendons with the unloaded control tendons and fresh tendons. Comparison across groups was assessed using one-way analysis of variance with the significance level set at ptendons that were exposed to cyclic load were significantly higher than those of unloaded control tendons. Acellularized tendon constructs that were reseeded with ASCs and exposed to a cyclic load had a UTS of 66.76 MPa and an EM of 906.68 MPa; their unloaded equivalents had a UTS of 47.90 MPa and an EM of 715.57 MPa. Similar trends were found in the fibroblast-seeded tendon constructs that were exposed to the bioreactor treatment. The bioreactor-treated tendons approached the UTS and EM values of fresh tendons. Histologically, we found that cells reoriented themselves parallel to the direction of strain in response to cyclic strain. The application of cyclic strain on seeded tendon constructs that were treated with the bioreactor helped achieve a UTS and an EM comparable with those of fresh tendons. Bioreactor pretreatment and alternative cell lines, such as ASCs and Fs, might therefore contribute to the in vitro production of strong tendon material. Copyright 2010. Published by Elsevier Inc.

  5. Comparative assessment of intrinsic mechanical stimuli on knee cartilage and compressed agarose constructs.

    Science.gov (United States)

    Completo, A; Bandeiras, C; Fonseca, F

    2017-06-01

    A well-established cue for improving the properties of tissue-engineered cartilage is mechanical stimulation. However, the explicit ranges of mechanical stimuli that correspond to favorable metabolic outcomes are elusive. Usually, these outcomes have only been associated with the applied strain and frequency, an oversimplification that can hide the fundamental relationship between the intrinsic mechanical stimuli and the metabolic outcomes. This highlights two important key issues: the firstly is related to the evaluation of the intrinsic mechanical stimuli of native cartilage; the second, assuming that the intrinsic mechanical stimuli will be important, deals with the ability to replicate them on the tissue-engineered constructs. This study quantifies and compares the volume of cartilage and agarose subjected to a given magnitude range of each intrinsic mechanical stimulus, through a numerical simulation of a patient-specific knee model coupled with experimental data of contact during the stance phase of gait, and agarose constructs under direct-dynamic compression. The results suggest that direct compression loading needs to be parameterized with time-dependence during the initial culture period in order to better reproduce each one of the intrinsic mechanical stimuli developed in the patient-specific cartilage. A loading regime which combines time periods of low compressive strain (5%) and frequency (0.5Hz), in order to approach the maximal principal strain and fluid velocity stimulus of the patient-specific cartilage, with time periods of high compressive strain (20%) and frequency (3Hz), in order to approach the pore pressure values, may be advantageous relatively to a single loading regime throughout the full culture period. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

  6. A regenerative biology view on artificial tissue construction and 3D bioprinting: what may we learn from natural regenerative phenomena?

    DEFF Research Database (Denmark)

    Lauridsen, Henrik

    2017-01-01

    organ structures by decellularisation/recellularisation procedures and recently with three-dimensional (3D) bioprinting show promising results in obtaining anatomically accurate constructs, however, the function of these artificial tissues is still lacking compared to natural tissues. This review...

  7. Cell-matrix mechanical interaction in electrospun polymeric scaffolds for tissue engineering: Implications for scaffold design and performance.

    Science.gov (United States)

    Kennedy, Kelsey M; Bhaw-Luximon, Archana; Jhurry, Dhanjay

    2017-03-01

    Engineered scaffolds produced by electrospinning of biodegradable polymers offer a 3D, nanofibrous environment with controllable structural, chemical, and mechanical properties that mimic the extracellular matrix of native tissues and have shown promise for a number of tissue engineering applications. The microscale mechanical interactions between cells and electrospun matrices drive cell behaviors including migration and differentiation that are critical to promote tissue regeneration. Recent developments in understanding these mechanical interactions in electrospun environments are reviewed, with emphasis on how fiber geometry and polymer structure impact on the local mechanical properties of scaffolds, how altering the micromechanics cues cell behaviors, and how, in turn, cellular and extrinsic forces exerted on the matrix mechanically remodel an electrospun scaffold throughout tissue development. Techniques used to measure and visualize these mechanical interactions are described. We provide a critical outlook on technological gaps that must be overcome to advance the ability to design, assess, and manipulate the mechanical environment in electrospun scaffolds toward constructs that may be successfully applied in tissue engineering and regenerative medicine. Tissue engineering requires design of scaffolds that interact with cells to promote tissue development. Electrospinning is a promising technique for fabricating fibrous, biomimetic scaffolds. Effects of electrospun matrix microstructure and biochemical properties on cell behavior have been extensively reviewed previously; here, we consider cell-matrix interaction from a mechanical perspective. Micromechanical properties as a driver of cell behavior has been well established in planar substrates, but more recently, many studies have provided new insights into mechanical interaction in fibrillar, electrospun environments. This review provides readers with an overview of how electrospun scaffold mechanics and

  8. Cell Patterning for Liver Tissue Engineering via Dielectrophoretic Mechanisms

    Directory of Open Access Journals (Sweden)

    Wan Nurlina Wan Yahya

    2014-07-01

    Full Text Available Liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a shortage of donors. Liver tissue engineering may offer an alternative by providing an implantable engineered liver. Currently, diverse types of engineering approaches for in vitro liver cell culture are available, including scaffold-based methods, microfluidic platforms, and micropatterning techniques. Active cell patterning via dielectrophoretic (DEP force showed some advantages over other methods, including high speed, ease of handling, high precision and being label-free. This article summarizes liver function and regenerative mechanisms for better understanding in developing engineered liver. We then review recent advances in liver tissue engineering techniques and focus on DEP-based cell patterning, including microelectrode design and patterning configuration.

  9. The construction of context-mechanisms-outcomes in realistic evaluation.

    Science.gov (United States)

    Linsley, Paul; Howard, David; Owen, Sara

    2015-01-01

    To discuss the construction of context-mechanisms-outcomes (CMOs) developed as part of a realistic evaluation study of two aggression management training programmes. Realistic evaluation draws on theories and methods derived from the social sciences. It provides a distinctive account of the nature of programmes and how they work. Realistic evaluation is a form of evaluation that is driven by theory, and was based by Pawson and Tilley ( 1997 ) on the philosophy of critical realism. Critical realism is an important perspective in modern philosophy and social science, but it is largely absent in the field of healthcare research. This paper provides a critical discussion on the construction of CMOs as part of a realistic evaluation study. This paper draws on the personal experiences of the author in using realistic evaluation to evaluate training in aggression management. Realistic evaluation stresses four key linked concepts for explaining and understanding programmes: 'mechanism', 'context', 'outcome pattern' and 'context-mechanisms-outcomes (CMO) pattern configuration'. A CMO configuration is a proposition stating what it is about an initiative that works, for whom and in what circumstances. In this way, the effectiveness of the programme is understood, with an explanation of why the outcomes developed as they did and how the programme was able to react to underlying mechanisms and in what contexts. Therefore, a realistic evaluation researcher is not just inspecting outcomes to see if an initiative (implementation) works, but is analysing the outcomes to discover if the conjectured mechanism or context theories are confirmed. This analysis provides not only evidence of effectiveness, but also an explanation that helps to develop and improve the content and the targeting of future programmes. The development of CMOs requires a great deal of skill on the part of the researcher and requires a flexibility of approach when collecting and analysing the data and in

  10. Scoria Cone Construction Mechanism, Lathrop Wells Volcano, Southern Nevada

    Energy Technology Data Exchange (ETDEWEB)

    G. Valentine; D. Krier; F. Perry; G. Heiken

    2005-01-18

    Scoria cones are commonly assumed to have been constructed by the accumulation of ballistically-ejected clasts from discrete and relatively coarse-grained Strombolian bursts and subsequent avalanching such that the cone slopes are at or near the angle of repose for loose scoria. The cone at the hawaiitic Lathrop Wells volcano, southern Nevada, contains deposits that are consistent with the above processes during early cone-building phases; these early deposits are composed mainly of coarse lapilli and fluidal bombs and are partially welded, indicating relatively little cooling during flight. However, the bulk of the cone is comprised of relatively fine-grained (ash and lapilli), planar beds with no welding, even within a few tens of meters of the vent. This facies is consistent with deposition by direct fallout from sustained eruption columns of relatively well-fragmented material, primarily mantling cone slopes and with a lesser degree of avalanching than is commonly assumed. A laterally extensive fallout deposit (up to 20 km from the vent) is inferred to have formed contemporaneously with these later cone deposits. This additional mechanism for construction of scoria cones may also be important at other locations, particularly where the magmas are relatively high in volatile content and where conditions promote the formation of abundant microlites in the rising mafic magma.

  11. [Construction of a capsular tissue-engineered ureteral stent seeded with autologous urothelial cells].

    Science.gov (United States)

    Tan, Haisong; Fu, Weijun; Li, Jianqiang; Wang, Zhongxin; Li, Gang; Ma, Xin; Dong, Jun; Gao, Jiangping; Wang, Xiaoxiong; Zhang, Xu

    2013-01-01

    To investigate the feasibility of constructing a capsular poly L-lactic acid (PLLA) ureteral stent seeded with autologous urothelial cells using tissue engineering methods. The capsular ureteral stent was constructed by subcutaneously embedding PLLA ureteral stent in the back of beagles for 3 weeks to induce the formation of connective tissue on the surfaces. After decellularization of the stent, the expanded autologous urothelial cells were seeded on the stent. The surface structure and cell adhesion of the stent were observed using HE staining, scanning electron microscope (SEM) and immunocytochemical staining. MTT assay was used to evaluate urothelial cell proliferation on the capsular PLLA ureteral stent and on circumferential small intestinal submucosa graft. HE staining and VIII factor immunohistochemistry revealed numerous capillaries in the connective tissue encapsulating the stent without obvious local inflammatory response. The results of SEM and immunocytochemical staining showed that the capsule contained rich collagenic fibers forming three-dimensional structures, and the seeded autologous urothelial cells could adhere and well aligned on the surface. MTT assay showed normal growth of the cells on the stent as compared with the cells grown on circumferential small intestinal submucosa graft. The capsular PLLA ureteral stent allows adhesion and proliferation of autologous urothelial cells and shows a potential in applications of constructing tissue-engineered ureter.

  12. Raman fiberoptic probe for monitoring human tissue engineered oral mucosa constructs

    Science.gov (United States)

    Khmaladze, Alexander; Kuo, Shiuhyang; Okagbare, Paul; Marcelo, Cynthia L.; Feinberg, Stephen E.; Morris, Michael D.

    2013-02-01

    In oral and maxillofacial surgery, there is a need for tissue engineered constructs for dental implants, reconstructions due to trauma, oral cancer or congenital defects. A non-invasive quality monitoring of the fabrication of tissue engineered constructs during their production and implantation is a required component of any successful tissue engineering technique. We demonstrate the design and application of a Raman spectroscopic probe for rapid and noninvasive monitoring of Ex Vivo Produced Oral Mucosa Equivalent constructs (EVPOMEs). We conducted in vivo studies to identify Raman spectroscopic failure indicators for EVPOMEs (already developed in vitro), and found that Raman spectra of EVPOMEs exposed to thermal stress showed correlation of the band height ratio of CH2 deformation to phenylalanine ring breathing modes, providing a Raman metric to distinguish between viable and nonviable constructs. This is the first step towards the ultimate goal to design a stand-alone system, which will be usable in a clinical setting, as the data processing and analysis will be performed with minimal user intervention, based on already established and tested Raman spectroscopic indicators for EVPOMEs.

  13. Advances in Application of Mechanical Stimuli in Bioreactors for Cartilage Tissue Engineering.

    Science.gov (United States)

    Li, Ke; Zhang, Chunqiu; Qiu, Lulu; Gao, Lilan; Zhang, Xizheng

    2017-08-01

    Articular cartilage (AC) is the weight-bearing tissue in diarthroses. It lacks the capacity for self-healing once there are injuries or diseases due to its avascularity. With the development of tissue engineering, repairing cartilage defects through transplantation of engineered cartilage that closely matches properties of native cartilage has become a new option for curing cartilage diseases. The main hurdle for clinical application of engineered cartilage is how to develop functional cartilage constructs for mass production in a credible way. Recently, impressive hyaline cartilage that may have the potential to provide capabilities for treating large cartilage lesions in the future has been produced in laboratories. The key to functional cartilage construction in vitro is to identify appropriate mechanical stimuli. First, they should ensure the function of metabolism because mechanical stimuli play the role of blood vessels in the metabolism of AC, for example, acquiring nutrition and removing wastes. Second, they should mimic the movement of synovial joints and produce phenotypically correct tissues to achieve the adaptive development between the micro- and macrostructure and function. In this article, we divide mechanical stimuli into three types according to forces transmitted by different media in bioreactors, namely forces transmitted through the liquid medium, solid medium, or other media, then we review and summarize the research status of bioreactors for cartilage tissue engineering (CTE), mainly focusing on the effects of diverse mechanical stimuli on engineered cartilage. Based on current researches, there are several motion patterns in knee joints; but compression, tension, shear, fluid shear, or hydrostatic pressure each only partially reflects the mechanical condition in vivo. In this study, we propose that rolling-sliding-compression load consists of various stimuli that will represent better mechanical environment in CTE. In addition, engineers

  14. Pattern of Bone Generation after Irradiation in Vascularized Tissue Engineered Constructs.

    Science.gov (United States)

    Eweida, Ahmad; Fathi, Ibrahim; Eltawila, Ahmed M; Elsherif, Ahmad M; Elkerm, Yasser; Harhaus, Leila; Kneser, Ulrich; Sakr, Mahmoud F

    2018-02-01

     Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization.  We investigated the pattern of bone formation in axially vascularized tissue engineering constructs (AVTECs) after irradiation in a study that mimics the clinical scenario after head and neck cancer. Heterotopic bone generation was induced in a subcutaneously implanted AVTEC in the thigh of six male New Zealand rabbits. The tissue construct was made up of Nanobone (Artoss GmbH; Rostock, Germany) granules mixed with autogenous bone marrow and 80 μL of bone morphogenic protein-2 at a concentration of 1.5 μg/μL. An arteriovenous loop was created microsurgically between the saphenous vessels and implanted in the core of the construct to induce axial vascularization. The constructs were subjected to external beam irradiation on postoperative day 20 with a single dose of 15 Gy. The constructs were removed 20 days after irradiation and subjected to histological and immunohistochemical analysis for vascularization, bone formation, apoptosis, and cellular proliferation.  The vascularized constructs showed homogenous vascularization and bone formation both in their central and peripheral regions. Although vascularity, proliferation, and apoptosis were similar between central and peripheral regions of the constructs, significantly more bone was formed in the central regions of the constructs.  The study shows for the first time the pattern of bone formation in AVTECs after irradiation using doses comparable to those applied after head and neck cancer. Axial vascularization probably enhances the osteoinductive properties in the central regions of AVTECs after irradiation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Autolysis: mechanisms of action in the removal of devitalised tissue.

    Science.gov (United States)

    Atkin, Leanne; Rippon, Mark

    2016-11-10

    Chronic wounds affect millions of people worldwide. In the UK alone, the cost of their treatment is estimated to be between £4.5bn and £5.1bn. The implementation of wound-bed preparation strategies remove the barriers to healing and wound debridement is a key component in preparing the wound bed for wound progression. This article aims to review one of the several debridement methods available to clinicians: autolytic debridement. Autolysis (i.e. autolytic debridement) uses the body's own enzymatic mechanisms to remove devitalised tissue in order to remove the barriers to healing. This review aims to provide clinicians working in wound care with a better understanding of the mechanisms and implications of autolytic debridement.

  16. A silk-based scaffold platform with tunable architecture for engineering critically-sized tissue constructs.

    Science.gov (United States)

    Wray, Lindsay S; Rnjak-Kovacina, Jelena; Mandal, Biman B; Schmidt, Daniel F; Gil, Eun Seok; Kaplan, David L

    2012-12-01

    In the field of tissue engineering and regenerative medicine there is significant unmet need for critically-sized, fully degradable biomaterial scaffold systems with tunable properties for optimizing tissue formation in vitro and tissue regeneration in vivo. To address this need, we have developed a silk-based scaffold platform that has tunable material properties, including localized and bioactive functionalization, degradation rate, and mechanical properties and that provides arrays of linear hollow channels for delivery of oxygen and nutrients throughout the scaffold bulk. The scaffolds can be assembled with dimensions that range from millimeters to centimeters, addressing the need for a critically-sized platform for tissue formation. We demonstrate that the hollow channel arrays support localized and confluent endothelialization. This new platform offers a unique and versatile tool for engineering 'tailored' scaffolds for a range of tissue engineering and regenerative medicine needs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. A continuum mechanics constitutive framework for transverse isotropic soft tissues

    Science.gov (United States)

    Garcia-Gonzalez, D.; Jérusalem, A.; Garzon-Hernandez, S.; Zaera, R.; Arias, A.

    2018-03-01

    In this work, a continuum constitutive framework for the mechanical modelling of soft tissues that incorporates strain rate and temperature dependencies as well as the transverse isotropy arising from fibres embedded into a soft matrix is developed. The constitutive formulation is based on a Helmholtz free energy function decoupled into the contribution of a viscous-hyperelastic matrix and the contribution of fibres introducing dispersion dependent transverse isotropy. The proposed framework considers finite deformation kinematics, is thermodynamically consistent and allows for the particularisation of the energy potentials and flow equations of each constitutive branch. In this regard, the approach developed herein provides the basis on which specific constitutive models can be potentially formulated for a wide variety of soft tissues. To illustrate this versatility, the constitutive framework is particularised here for animal and human white matter and skin, for which constitutive models are provided. In both cases, different energy functions are considered: Neo-Hookean, Gent and Ogden. Finally, the ability of the approach at capturing the experimental behaviour of the two soft tissues is confirmed.

  18. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  19. Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers

    International Nuclear Information System (INIS)

    Levato, Riccardo; Planell, Josep A; Engel, Elisabeth; Visser, Jetze; Malda, Jos; Mateos-Timoneda, Miguel A

    2014-01-01

    Bioprinting allows the fabrication of living constructs with custom-made architectures by spatially controlled deposition of multiple bioinks. This is important for the generation of tissue, such as osteochondral tissue, which displays a zonal composition in the cartilage domain supported by the underlying subchondral bone. Challenges in fabricating functional grafts of clinically relevant size include the incorporation of cues to guide specific cell differentiation and the generation of sufficient cells, which is hard to obtain with conventional cell culture techniques. A novel strategy to address these demands is to combine bioprinting with microcarrier technology. This technology allows for the extensive expansion of cells, while they form multi-cellular aggregates, and their phenotype can be controlled. In this work, living constructs were fabricated via bioprinting of cell-laden microcarriers. Mesenchymal stromal cell (MSC)-laden polylactic acid microcarriers, obtained via static culture or spinner flask expansion, were encapsulated in gelatin methacrylamide-gellan gum bioinks, and the printability of the composite material was studied. This bioprinting approach allowed for the fabrication of constructs with high cell concentration and viability. Microcarrier encapsulation improved the compressive modulus of the hydrogel constructs, facilitated cell adhesion, and supported osteogenic differentiation and bone matrix deposition by MSCs. Bilayered osteochondral models were fabricated using microcarrier-laden bioink for the bone compartment. These findings underscore the potential of this new microcarrier-based biofabrication approach for bone and osteochondral constructs. (paper)

  20. Mechanical characterization and structural assessment of biocomposites for construction

    Science.gov (United States)

    Christian, Sarah Jane

    The objective of this dissertation is to assess whether or not two particular biocomposite materials, made from hemp fabric and cellulose acetate or polyhydroxybutyrate matrices, are capable of being used for structural and/or construction purposes within in the construction and building industry. The objective of this dissertation was addressed by conducting research to meet the following three goals: (1) to measure the basic mechanical properties of hemp/cellulose acetate and hemp/PHB biocomposites and evaluate if they suitable for use in construction applications, (2) to determine how quickly moisture diffuses into the biocomposite materials and how the moisture affects the mechanical behavior, and (3) to determine how well simple models can predict behavior of structural scale laminates in tension and flexure using biocomposite ply behavior. Compression molding was used to manufacturing the biocomposites from hemp fabric and the themoplastic matrices: cellulose acetate and polyhydroxybutyrate. Four methods for determining the fiber volume fraction were evaluated, and the dissolution method, using different solvents for each matrix type, was used to determine the fiber volume fraction for each composite plate manufactured. Both types of biocomposite were tested in tension, compression, shear, and flexure and the measured properties were compared to wood and engineered wood products to assess whether the biocomposite properties are suitable for use in the construction industry. The biocomposites were conditioned in a humid environment to determine the rate of moisture diffusion into the materials. Then saturated specimens and specimens that were saturated and then dried were tested in tension to evaluate how moisture absorption affects the mechanical behavior of the biocomposites. Finally, simple models of laminate behavior based on laminate plate theory were evaluated to determine if ply level behavior could be used to predict structural scale laminate behavior

  1. A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue Constructs.

    Science.gov (United States)

    Athirasala, Avathamsa; Lins, Fernanda; Tahayeri, Anthony; Hinds, Monica; Smith, Anthony J; Sedgley, Christine; Ferracane, Jack; Bertassoni, Luiz E

    2017-06-12

    The requirement for immediate vascularization of engineered dental pulp poses a major hurdle towards successful implementation of pulp regeneration as an effective therapeutic strategy for root canal therapy, especially in adult teeth. Here, we demonstrate a novel strategy to engineer pre-vascularized, cell-laden hydrogel pulp-like tissue constructs in full-length root canals for dental pulp regeneration. We utilized gelatin methacryloyl (GelMA) hydrogels with tunable physical and mechanical properties to determine the microenvironmental conditions (microstructure, degradation, swelling and elastic modulus) that enhanced viability, spreading and proliferation of encapsulated odontoblast-like cells (OD21), and the formation of endothelial monolayers by endothelial colony forming cells (ECFCs). GelMA hydrogels with higher polymer concentration (15% w/v) and stiffness enhanced OD21 cell viability, spreading and proliferation, as well as endothelial cell spreading and monolayer formation. We then fabricated pre-vascularized, full-length, dental pulp-like tissue constructs by dispensing OD21 cell-laden GelMA hydrogel prepolymer in root canals of extracted teeth and fabricating 500 µm channels throughout the root canals. ECFCs seeded into the microchannels successfully formed monolayers and underwent angiogenic sprouting within 7 days in culture. In summary, the proposed approach is a simple and effective strategy for engineering of pre-vascularized dental pulp constructs offering potentially beneficial translational outcomes.

  2. CONSTRUCTION SELF-PROPELLED PNEUMOPUNCHERS WITH LOCKING MECHANISM

    Directory of Open Access Journals (Sweden)

    V. K. Perederey

    2016-01-01

    Full Text Available The paper reveals one of possible methods for higher productivity and reliability of building self-propelled pneumopunchers which are intended for making holes in soil while using trenchless method and constructing various engineering communications under car, tram and rail lines, airport runways. A new design of building pneumopuncher with increased productivity due to higher speed for hole formation in soil and its reliability has been presented in the paper. A formula for determination of displacement increment for a new pneumopuncher in comparison with the conventional one has been obtained in the paper. The paper describes a design and operation principal of the building self-propelled pneumopuncher which is equipped with a locking mechanism with the purpose to neutralize action of soil elastic forces and reactive repulsive force. The locking mechanism keeps the pneumopuncher in the hole. The pneumopuncher consists of a body with anvil, movable hammer, a manifold which is set in axial deepening of the hammer, a nut and a locking mechanism. Improvement of operational pneumopuncher reliability is attained due to the fact that the locking mechanism is made in the form of two coaxially positioned inner and outer cups having a common basis. A piston is installed in the middle of the inner cup, a spring is fixed over the piston and a rod with a breaking shoe is positioned at the end. Height of the inner cup is less the outer cup height and there is an annular cavity between them which is connected with a chamber. The chamber is formed by the piston, the inner cup and the manifold. The annular cavity through an opening in the inner cup wall, two sylphons, a channel in the nut end and an opening in the vertical wall of the manifold are connected with a chamber of operating stroke. The sylphons are placed between the outer cup and the nut, between the nut and the manifold. Differential equations for movement of pneumopuncher in soil have been

  3. Characterization of tissue-equivalent materials for use in construction of physical phantoms

    International Nuclear Information System (INIS)

    Souza, Edvan V. de; Oliveira, Alex C.H. de; Vieira, Jose W.; Lima, Fernando R.A.

    2013-01-01

    Phantoms are physical or computational models used to simulate the transport of ionizing radiation, their interactions with human body tissues and evaluate the deposition of energy. Depending on the application, you can build phantoms of various types and features. The physical phantoms are made of materials with behavior similar to human tissues exposed to ionizing radiation, the so-called tissue-equivalent materials. The characterization of various tissue-equivalent materials is important for the choice of materials to be used is appropriate, seeking a better cost-benefit ratio. The main objective of this work is to produce tables containing the main characteristics of tissue-equivalent materials. These tables were produced in Microsoft Office Excel. Among the main features of tissue-equivalent materials that were added to the tables, are density, chemical composition, physical state, chemical stability and solubility. The main importance of this work is to contribute to the construction of high-quality physical phantoms and avoid the waste of materials

  4. Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs

    Science.gov (United States)

    Wang, Bo; Patnaik, Sourav S.; Brazile, Bryn; Butler, J. Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

    2016-01-01

    Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications. PMID:27480586

  5. A mathematical model for fluid shear-sensitive 3D tissue construct development.

    Science.gov (United States)

    Liu, Dan; Chua, Chee-Kai; Leong, Kah-Fai

    2013-01-01

    This research studies dynamic culture for 3D tissue construct development with computational fluid dynamics. It proposes a mathematical model to evaluate the impact of flow rates and flow shear stress on cell growth in 3D constructs under perfusion. The modeling results show that dynamic flow, even at flow rate as low as 0.002 cm/s, can support much better mass exchange, higher cell number, and more even cell and nutrient distribution compared to static culture. Higher flow rate can further improve nutrient supply and mass exchange in the construct, promoting better nutritious environment and cell proliferation compared to lower flow rate. In addition, consideration of flow shear stress predicts much higher cell number in the construct compared to that without shear consideration. While the nutrient can dominate shear stress in influencing cell proliferation, the shear effect increases with flow rate. The proposed model helps tissue engineers better understand the cell-flow relationship at the molecular level during dynamic culture.

  6. Probing embryonic tissue mechanics with laser hole drilling

    International Nuclear Information System (INIS)

    Ma Xiaoyan; Lynch, Holley E; Scully, Peter C; Hutson, M Shane

    2009-01-01

    We use laser hole drilling to assess the mechanics of an embryonic epithelium during development—in vivo and with subcellular resolution. We ablate a subcellular cylindrical hole clean through the epithelium and track the subsequent recoil of adjacent cells (on ms time scales). We investigate dorsal closure in the fruit fly with emphasis on apical constriction of amnioserosa cells. The mechanical behavior of this epithelium falls between that of a continuous sheet and a 2D cellular foam (a network of tensile interfaces). Tensile stress is carried both by cell–cell interfaces and by the cells' apical actin networks. Our results show that stress is slightly concentrated along interfaces (1.6-fold), but only in early closure. Furthermore, closure is marked by a decrease in the recoil power-law exponent, implying a transition to a more solid-like tissue. We use the site and stage dependence of the recoil kinetics to constrain how the cellular mechanics change during closure. We apply these results to test extant computational models

  7. Dynamic environmental control mechanisms for pneumatic foil constructions

    Science.gov (United States)

    Flor, Jan-Frederik; Wu, Yupeng; Beccarelli, Paolo; Chilton, John

    2017-11-01

    Membrane and foil structures have become over the last decades an attractive alternative to conventional materials and building systems with increasing implementation in different typologies and scale. The development of transparent, light, flexible and resistant materials like Ethylene Tetrafluoroethylene (ETFE) has triggered a rethinking of the building envelope in the building industry towards lightweight systems. ETFE foil cushions have proven to fulfil the design requirements in terms of structural efficiency and aesthetic values. But the strategies to satisfy increasing demands of energy efficiency and comfort conditions are still under development. The prediction and manipulation of the thermo-optical behaviour of ETFE foil cushion structures currently remain as one of the main challenges for designers and manufacturers. This paper reviews ongoing research regarding the control of the thermo-optical performance of ETFE cushion structures and highlights challenges and possible improvements. An overview of different dynamic and responsive environmental control mechanisms for multilayer foil constructions is provided and the state of the art in building application outlined by the discussion of case studies.

  8. [Experimental study of tissue engineered cartilage construction using oriented scaffold combined with bone marrow mesenchymal stem cells in vivo].

    Science.gov (United States)

    Duan, Wei; Da, Hu; Wang, Wentao; Lü, Shangjun; Xiong, Zhuo; Liu, Jian

    2013-05-01

    To investigate the feasibility of fabricating an oriented scaffold combined with chondrogenic-induced bone marrow mesenchymal stem cells (BMSCs) for enhancement of the biomechanical property of tissue engineered cartilage in vivo. Temperature gradient-guided thermal-induced phase separation was used to fabricate an oriented cartilage extracellular matrix-derived scaffold composed of microtubules arranged in parallel in vertical section. No-oriented scaffold was fabricated by simple freeze-drying. Mechanical property of oriented and non-oriented scaffold was determined by measurement of compressive modulus. Oriented and non-oriented scaffolds were seeded with chondrogenic-induced BMSCs, which were obtained from the New Zealand white rabbits. Proliferation, morphological characteristics, and the distribution of the cells on the scaffolds were analyzed by MTT assay and scanning electron microscope. Then cell-scaffold composites were implanted subcutaneously in the dorsa of nude mice. At 2 and 4 weeks after implantation, the samples were harvested for evaluating biochemical, histological, and biomechanical properties. The compressive modulus of oriented scaffold was significantly higher than that of non-oriented scaffold (t=201.099, P=0.000). The cell proliferation on the oriented scaffold was significantly higher than that on the non-oriented scaffold from 3 to 9 days (P fibers with chondrocyte-like cells on the oriented-structure constructs. Total DNA, glycosaminoglycan (GAG), and collagen contents increased with time, and no significant difference was found between 2 groups (P > 0.05). The compressive modulus of the oriented tissue engineered cartilage was significantly higher than that of the non-oriented tissue engineered cartilage at 2 and 4 weeks after implantation (P < 0.05). Total DNA, GAG, collagen contents, and compressive modulus in the 2 tissue engineered cartilages were significantly lower than those in normal cartilage (P < 0.05). Oriented extracellular

  9. Construction and characterization of a cDNA library from human liver tissue with chronic hepatitis B.

    Science.gov (United States)

    Chen, Xiao-hong; Chen, Zhi; Yao, Hang-ping; Chen, Feng; Zhu, Hai-hong; Zhou, Hong-juan

    2005-04-01

    To construct a cDNA library from human liver tissue with chronic hepatitis B and check its quality for investigating the expression level of liver tissue infected by hepatitis B virus. This will then be used to find the relevant genes and interesting proteins associated with the development of hepatitis B. The total RNA from liver tissue with chronic hepatitis B was extracted and the mRNA was purified using TRIZOL method. Switching mechanism at 5' end of the RNA transcript (SMART) technique and CDS III/3' primer were used for first-strand cDNA synthesis. Long distance polymerase chain reaction (LD PCR) was then used to synthesize the double-strand cDNA that was then digested by Sfi I and fractionated by CHROMA SPIN-400 column. The longer than 0.4 kb cDNAs were collected and ligated to lambdaTriplEx2 vector. Then lambda phage packaging reaction and library amplification were performed. The qualities of both unamplified and amplified cDNA libraries were strictly checked by conventional titer determination. Fourteen plaques were randomly picked and tested using PCR with universal primers derived from the sequence flanking the vector. The titers of unamplifed and amplified libraries were 1.94 x 10(6) pfu/ml and 1.49 x 10(9) pfu/ml respectively. The percentages of recombinants from both libraries were 98.15% in unamplified library and 98.76% in amplified library. The lengths of the inserts were 1.23 kb in average, 1-2 kb in 64.29%, and 0.5-1.0 kb in 35.71%. A high quality cDNA library from human liver tissue with chronic hepatitis B was successfully constructed.

  10. Monitoring Bone Tissue Engineered (BTE) Constructs Based on the Shifting Metabolism of Differentiating Stem Cells.

    Science.gov (United States)

    Simmons, Aaron D; Sikavitsas, Vassilios I

    2018-01-01

    Ever-increasing demand for bone grafts necessitates the realization of clinical implementation of bone tissue engineered constructs. The predominant hurdle to implementation remains to be securing FDA approval, based on the lack of viable methods for the rigorous monitoring of said constructs. The study presented herein details a method for such monitoring based on the shifting metabolism of mesenchymal stem cells (MSCs) as they differentiate into osteoblasts. To that end, rat MSCs seeded on 85% porous spunbonded poly(L-lactic acid) scaffolds were cultured in flow perfusion bioreactors with baseline or osteoinductive media, and levels of key physio-metabolic markers (oxygen, glucose, osteoprotegerin, and osteocalcin) were monitored throughout culture. Comparison of these non-destructively obtained values and current standard destructive analyses demonstrated key trends useful for the concurrent real-time monitoring of construct cellularity and maturation. Principle among these is the elucidation of the ratio of the rates of oxygen uptake to glucose consumption as a powerful quality marker. This ratio, supported on a physiological basis, has been shown herein to be reliable in the determination of both construct maturation (defined as osteoblastic differentiation and accompanying mineralization) and construct cellularity. Supplementary monitoring of OPG and OCN are shown to provide further validation of such metrics.

  11. A native-like corneal construct using donor corneal stroma for tissue engineering.

    Directory of Open Access Journals (Sweden)

    Jing Lin

    Full Text Available Tissue engineering holds great promise for corneal transplantation to treat blinding diseases. This study was to explore the use of natural corneal stroma as an optimal substrate to construct a native like corneal equivalent. Human corneal epithelium was cultivated from donor limbal explants on corneal stromal discs prepared by FDA approved Horizon Epikeratome system. The morphology, phenotype, regenerative capacity and transplantation potential were evaluated by hematoxylin eosin and immunofluorescent staining, a wound healing model, and the xeno-transplantation of the corneal constructs to nude mice. An optically transparent and stratified epithelium was rapidly generated on donor corneal stromal substrate and displayed native-like morphology and structure. The cells were polygonal in the basal layer and became flattened in superficial layers. The epithelium displayed a phenotype similar to human corneal epithelium in vivo. The differentiation markers, keratin 3, involucrin and connexin 43, were expressed in full or superficial layers. Interestingly, certain basal cells were immunopositive to antibodies against limbal stem/progenitor cell markers ABCG2 and p63, which are usually negative in corneal epithelium in vivo. It suggests that this bioengineered corneal epithelium shared some characteristics of human limbal epithelium in vivo. This engineered epithelium was able to regenerate in 4 days following from a 4mm-diameter wound created by a filter paper soaked with 1 N NaOH. This corneal construct survived well after xeno-transplantation to the back of a nude mouse. The transplanted epithelium remained multilayer and became thicker with a phenotype similar to human corneal epithelium. Our findings demonstrate that natural corneal stroma is an optimal substrate for tissue bioengineering, and a native-like corneal construct has been created with epithelium containing limbal stem cells. This construct may have great potential for clinical use in

  12. Biological and mechanical evaluation of a Bio-Hybrid scaffold for autologous valve tissue engineering.

    Science.gov (United States)

    Jahnavi, S; Saravanan, U; Arthi, N; Bhuvaneshwar, G S; Kumary, T V; Rajan, S; Verma, R S

    2017-04-01

    Major challenge in heart valve tissue engineering for paediatric patients is the development of an autologous valve with regenerative capacity. Hybrid tissue engineering approach is recently gaining popularity to design scaffolds with desired biological and mechanical properties that can remodel post implantation. In this study, we fabricated aligned nanofibrous Bio-Hybrid scaffold made of decellularized bovine pericardium: polycaprolactone-chitosan with optimized polymer thickness to yield the desired biological and mechanical properties. CD44 + , αSMA + , Vimentin + and CD105 - human valve interstitial cells were isolated and seeded on these Bio-Hybrid scaffolds. Subsequent biological evaluation revealed interstitial cell proliferation with dense extra cellular matrix deposition that indicated the viability for growth and proliferation of seeded cells on the scaffolds. Uniaxial mechanical tests along axial direction showed that the Bio-Hybrid scaffolds has at least 20 times the strength of the native valves and its stiffness is nearly 3 times more than that of native valves. Biaxial and uniaxial mechanical studies on valve interstitial cells cultured Bio-Hybrid scaffolds revealed that the response along the axial and circumferential direction was different, similar to native valves. Overall, our findings suggest that Bio-Hybrid scaffold is a promising material for future development of regenerative heart valve constructs in children. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Application and Mechanics Analysis of Multi-Function Construction Platforms in Prefabricated-Concrete Construction

    Science.gov (United States)

    Wang, Meihua; Li, Rongshuai; Zhang, Wenze

    2017-11-01

    Multi-function construction platforms (MCPs) as an “old construction technology, new application” of the building facade construction equipment, its efforts to reduce labour intensity, improve labour productivity, ensure construction safety, shorten the duration of construction and other aspects of the effect are significant. In this study, the functional analysis of the multi-function construction platforms is carried out in the construction of the assembly building. Based on the general finite element software ANSYS, the static calculation and dynamic characteristics analysis of the MCPs structure are analysed, the simplified finite element model is constructed, and the selection of the unit, the processing and solution of boundary are under discussion and research. The maximum deformation value, the maximum stress value and the structural dynamic characteristic model are obtained. The dangerous parts of the platform structure are analysed, too. Multiple types of MCPs under engineering construction conditions are calculated, so as to put forward the rationalization suggestions for engineering application of the MCPs.

  14. Construction of functional tissue-engineered bone using cell sheet technology in a canine model.

    Science.gov (United States)

    Chen, Tao; Wang, Yanhui; Bu, Lingxue; Li, Ningyi

    2014-04-01

    The aim of the present study was to construct functional tissue-engineered bone with cell sheet technology and compare the efficacy of this method with that of traditional bone tissue engineering techniques. Canine bone mesenchymal stem cells (BMSCs) were isolated using density gradient centrifugation and then cultured. The BMSCs were induced to differentiate into osteoblasts and cultured in temperature-responsive culture dishes. The BMSCs detached automatically from the temperature-responsive culture dishes when the temperature was reduced to 20°C, forming an intact cell sheet. Demineralized bone matrix (DBM) and platelet-rich plasma (PRP) were prepared and used to construct a DBM/PRP/BMSC cell sheet/BMSC complex, which was implanted under the left latissimus dorsi muscle in a dog model. A DBM/PRP/BMSC complex was used as a control and implanted under the right latissimus dorsi muscle in the dog model. Immunoblot assays were performed to detect the levels of growth factors. Osteogenesis was observed to be induced significantly more effectively in the DBM/PRP/BMSC cell sheet/BMSC implants than in the DBM/PRP/BMSC implants. Immunoblot assay results indicated that the levels of the growth factors platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) in the experimental group were 3.2- and 2.5-fold higher compared with those in the control group, respectively. These results indicated that the BMSC cell sheets were functional and more effective than the control cell complex. Therefore, cell sheet technology may be used for the effective construction of functional tissue-engineered bone with ideal properties.

  15. Connective Tissue Degeneration: Mechanisms of Palmar Fascia Degeneration (Dupuytren's Disease)

    NARCIS (Netherlands)

    Karkampouna, S.; Kreulen, M.; Obdeijn, M. C.; Kloen, P.; Dorjée, A. L.; Rivellese, F.; Chojnowski, A.; Clark, I.; Kruithof-de Julio, Marianna

    2016-01-01

    Dupuytren's disease is a connective tissue disorder of the hand causing excessive palmar fascial fibrosis with associated finger contracture and disability. The aetiology of the disease is heterogeneous, with both genetic and environmental components. The connective tissue is abnormally infiltrated

  16. [Construction of 3D tissue-like structure using functional magnetite nanoparticles].

    Science.gov (United States)

    Ito, Akira; Honda, Hiroyuki; Kamihira, Masamichi

    2008-01-01

    Magnetic nanoparticles for medical applications have been developed by many researchers. Since these nanoparticles have unique magnetic features not present in other materials, they can be applied to special medical techniques. Magnetite cationic liposomes (MCLs), one group of the cationic magnetic particles, can be used as carriers to introduce magnetite nanoparticles into target cells since their positively charged surface interacts with the negatively charged cell surface. Magnetite nanoparticles conjugated with antibodies (antibody-conjugated magnetoliposomes, AMLs) are applicable to introduce magnetite nanoparticles specifically into target cells, even when target cells coexist with other kinds of cells. Since the cells labeled with magnetite nanoparticles could be manipulated using magnets, we applied this technique to tissue engineering and termed it ;magnetic force-based tissue engineering (Mag-TE)'. Both magnetic force and functionalized magnetite nanoparticles were used in a process of tissue engineering: construction of multilayered cell sheet-like structures and tubular structures. Thus, the applications of these functionalized magnetite nanoparticles with their unique features will further improve tissue engineering techniques.

  17. Construction and evaluation of urinary bladder bioreactor for urologic tissue-engineering purposes.

    LENUS (Irish Health Repository)

    Davis, Niall F

    2012-01-31

    OBJECTIVE: To design and construct a urinary bladder bioreactor for urologic tissue-engineering purposes and to compare the viability and proliferative activity of cell-seeded extracellular matrix scaffolds cultured in the bioreactor with conventional static growth conditions. MATERIALS AND METHODS: A urinary bladder bioreactor was designed and constructed to replicate physiologic bladder dynamics. The bioreactor mimicked the filling pressures of the human bladder by way of a cyclical low-delivery pressure regulator. In addition, cell growth was evaluated by culturing human urothelial cells (UCs) on porcine extracellular matrix scaffolds in the bioreactor and in static growth conditions for 5 consecutive days. The attachment, viability, and proliferative potential were assessed and compared with quantitative viability indicators and by fluorescent markers for intracellular esterase activity and plasma membrane integrity. Scaffold integrity was characterized with scanning electron microscopy and 4\\

  18. Multilayer cell-seeded polymer nanofiber constructs for soft-tissue reconstruction.

    Science.gov (United States)

    Barker, Daniel A; Bowers, Daniel T; Hughley, Brian; Chance, Elizabeth W; Klembczyk, Kevin J; Brayman, Kenneth L; Park, Stephen S; Botchwey, Edward A

    2013-09-01

    Cell seeding throughout the thickness of a nanofiber construct allows for patient-specific implant alternatives with long-lasting effects, earlier integration, and reduced inflammation when compared with traditional implants. Cell seeding may improve implant integration with host tissue; however, the effect of cell seeding on thick nanofiber constructs has not been studied. To use a novel cell-preseeded nanofiber tissue engineering technique to create a 3-dimensional biocompatible implant alternative to decellularized extracellular matrix. Animal study with mammalian cell culture to study tissue engineered scaffolds. Academic research laboratory. Thirty-six Sprague-Dawley rats. The rats each received 4 implant types. The grafts included rat primary (enhanced green fluorescent protein-positive [eGFP+]) fibroblast-seeded polycaprolactone (PCL)/collagen nanofiber scaffold, PCL/collagen cell-free nanofiber scaffold, acellular human cadaveric dermis (AlloDerm), and acellular porcine dermis (ENDURAGen). Rats were monitored postoperatively and received enrofloxacin in the drinking water for 4 days prophylactically and buprenorphine (0.2-0.5 mg/kg administered subcutaneously twice a day postoperatively for pain for 48 hours). The viability of NIH/3T3 fibroblasts cultured on PCL electrospun nanofibers was evaluated using fluorescence microscopy. Soft-tissue remodeling was examined histologically and with novel ex vivo volume determinations of implants using micro-computed tomography of cell-seeded implants relative to nanofibers without cells and commonly used dermal grafts of porcine and human origin (ENDURAGen and AlloDerm, respectively). The fate and distribution of eGFP+ seeded donor fibroblasts were assessed using immunohistochemistry. Fibroblasts migrated across nanofiber layers within 12 hours and remained viable on a single layer for up to 14 days. Scanning electron microscopy confirmed a nanoscale structure with a mean (SD) diameter of 158 (72) nm. Low extrusion

  19. Mechanisms of Regulating Tissue Elongation in Drosophila Wing: Impact of Oriented Cell Divisions, Oriented Mechanical Forces, and Reduced Cell Size

    Science.gov (United States)

    Li, Yingzi; Naveed, Hammad; Kachalo, Sema; Xu, Lisa X.; Liang, Jie

    2014-01-01

    Regulation of cell growth and cell division plays fundamental roles in tissue morphogenesis. However, the mechanisms of regulating tissue elongation through cell growth and cell division are still not well understood. The wing imaginal disc of Drosophila provides a model system that has been widely used to study tissue morphogenesis. Here we use a recently developed two-dimensional cellular model to study the mechanisms of regulating tissue elongation in Drosophila wing. We simulate the effects of directional cues on tissue elongation. We also computationally analyze the role of reduced cell size. Our simulation results indicate that oriented cell divisions, oriented mechanical forces, and reduced cell size can all mediate tissue elongation, but they function differently. We show that oriented cell divisions and oriented mechanical forces act as directional cues during tissue elongation. Between these two directional cues, oriented mechanical forces have a stronger influence than oriented cell divisions. In addition, we raise the novel hypothesis that reduced cell size may significantly promote tissue elongation. We find that reduced cell size alone cannot drive tissue elongation. However, when combined with directional cues, such as oriented cell divisions or oriented mechanical forces, reduced cell size can significantly enhance tissue elongation in Drosophila wing. Furthermore, our simulation results suggest that reduced cell size has a short-term effect on cell topology by decreasing the frequency of hexagonal cells, which is consistent with experimental observations. Our simulation results suggest that cell divisions without cell growth play essential roles in tissue elongation. PMID:24504016

  20. Integrated-mechanized production of welded constructions in boiler fabrication and nuclear power engineering

    International Nuclear Information System (INIS)

    Medal'e, V.G.; Shul'man, I.E.; Shcherbatykh, V.A.

    1981-01-01

    Modern state and prospects of development of integral- mechanized production of welded constructions in boiler fabrication and nuclear power engineering are considered. Several integral-mechanized sections being under operation at the enterprises of the branch of industry are described. Efficiency of the use of integral-mechanized production of welded constructions is shown [ru

  1. Mechanical characterization of stomach tissue under uniaxial tensile action.

    Science.gov (United States)

    Jia, Z G; Li, W; Zhou, Z R

    2015-02-26

    In this article, the tensile properties of gastric wall were investigated by using biomechanical test and theoretical analysis. The samples of porcine stomach strips from smaller and greater curvature of the stomach were cut in longitudinal and circumferential direction, respectively. The loading-unloading, stress relaxation, strain creep, tensile fracture tests were performed at mucosa-submucosa, serosa-muscle and intact layer, respectively. Results showed that the biomechanical properties of the porcine stomach depended on the layers, orientations and locations of the gastric wall and presented typical viscoelastic, nonlinear and anisotropic mechanical properties. During loading-unloading test, the stress of serosa-muscle layer in the longitudinal direction was 15-20% more than that in the circumferential direction at 12% stretch ratio, while it could reach about 40% for the intact layer and 50% for the mucosa-submucosa layer. The results of stress relaxation and strain creep showed that the variation degree was obviously faster in the circumferential direction than that in the longitudinal direction, and the ultimate residual values were also different for the different layers, orientations and locations. In the process of fracture test, the serosa-muscle layer fractured firstly followed by the mucosa-submucosa layer when the intact layer was tested, the longitudinal strips firstly began to fracture and the required stress value was about twice as much as that in the circumferential strips. The anisotropy and heterogeneity of mechanical characterization of the porcine stomach were related to its complicated geometry, structure and functions. The results would help us to understand the biomechanics of soft organ tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Alternative mechanism for white adipose tissue lipolysis after thermal injury.

    Science.gov (United States)

    Diao, Li; Patsouris, David; Sadri, Ali-Reza; Dai, Xiaojing; Amini-Nik, Saeid; Jeschke, Marc G

    2015-12-29

    Extensively burned patients often suffer from sepsis, a complication that enhances post-burn hypermetabolism and contributes to increased incidence of multiple organ failure, morbidity and mortality. Despite the clinical importance of burn sepsis, the molecular and cellular mechanisms of such infection-related metabolic derangements and organ dysfunction are still largely unknown. We recently found that upon endoplasmic reticulum (ER) stress, the white adipose tissue (WAT) interacts with the liver via inflammatory and metabolic signals leading to profound hepatic alterations, including hepatocyte apoptosis and hepatic fatty infiltration. We therefore hypothesized that burn plus infection causes an increase in lipolysis of WAT after major burn, partially through induction of ER stress, contributing to hyperlipidemia and profound hepatic lipid infiltration. We used a two-hit rat model of 60% total body surface area scald burn, followed by intraperitoneal injection of Pseudomonas Aeruginosa-derived lipopolysaccharide (LPS) 3 days post-burn. One day later, animals were sacrificed and liver and epididymal WAT (EWAT) samples were collected for gene expression, protein analysis and histological study of inflammasome activation, ER stress, apoptosis and lipid metabolism. Our results showed that burn plus LPS profoundly increased lipolysis in WAT associated with significantly increased hepatic lipid infiltration. Burn plus LPS augmented ER stress by upregulating CHOP and activating ATF6, inducing NLRP3 inflammasome activation and leading to increased apoptosis and lipolysis in WAT with a distinct enzymatic mechanism related to inhibition of AMPK signaling. In conclusion, burn sepsis causes profound alterations in WAT and liver which are associated with changes in organ function and structure.

  3. How Tissue Mechanical Properties Affect Enteric Neural Crest Cell Migration

    Science.gov (United States)

    Chevalier, N. R.; Gazguez, E.; Bidault, L.; Guilbert, T.; Vias, C.; Vian, E.; Watanabe, Y.; Muller, L.; Germain, S.; Bondurand, N.; Dufour, S.; Fleury, V.

    2016-02-01

    Neural crest cells (NCCs) are a population of multipotent cells that migrate extensively during vertebrate development. Alterations to neural crest ontogenesis cause several diseases, including cancers and congenital defects, such as Hirschprung disease, which results from incomplete colonization of the colon by enteric NCCs (ENCCs). We investigated the influence of the stiffness and structure of the environment on ENCC migration in vitro and during colonization of the gastrointestinal tract in chicken and mouse embryos. We showed using tensile stretching and atomic force microscopy (AFM) that the mesenchyme of the gut was initially soft but gradually stiffened during the period of ENCC colonization. Second-harmonic generation (SHG) microscopy revealed that this stiffening was associated with a gradual organization and enrichment of collagen fibers in the developing gut. Ex-vivo 2D cell migration assays showed that ENCCs migrated on substrates with very low levels of stiffness. In 3D collagen gels, the speed of the ENCC migratory front decreased with increasing gel stiffness, whereas no correlation was found between porosity and ENCC migration behavior. Metalloprotease inhibition experiments showed that ENCCs actively degraded collagen in order to progress. These results shed light on the role of the mechanical properties of tissues in ENCC migration during development.

  4. Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering.

    Science.gov (United States)

    Mirahmadi, Fereshteh; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali; Bonakdar, Shahin

    2013-12-01

    Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber-hydrogel composite for GAG content and in two-layer electrospun fiber-hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. © 2013.

  5. Quantifying the mechanics of embryonic tissues in vivo and in situ

    Science.gov (United States)

    Campas, Otger

    The sculpting of tissues and organs involves a tight spatiotemporal regulation of several physical fields, including active mechanical stresses and the local material properties. Despite the relevance of mechanics in embryonic morphogenesis, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify mechanics within developing tissues in vivo and in situ. I will present two new techniques that permit direct quantification of (1) mechanical stresses at both tissue and cellular scales and (2) the material properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we characterize the mechanics of cell aggregates (in vitro), living mouse mandibles (ex vivo) and live zebrafish embryonic tissues (in vivo).

  6. Bioinspired coupled helical coils for soft tissue engineering of tubular structures - Improved mechanical behavior of tubular collagen type I templates.

    Science.gov (United States)

    Janke, H P; Bohlin, J; Lomme, R M L M; Mihaila, S M; Hilborn, J; Feitz, W F J; Oosterwijk, E

    2017-09-01

    The design of constructs for tubular tissue engineering is challenging. Most biomaterials need to be reinforced with supporting structures such as knittings, meshes or electrospun material to comply with the mechanical demands of native tissues. In this study, coupled helical coils (CHCs) were manufactured to mimic collagen fiber orientation as found in nature. Monofilaments of different commercially available biodegradable polymers were wound and subsequently fused, resulting in right-handed and left-handed polymer helices fused together in joints where the filaments cross. CHCs of different polymer composition were tested to determine the tensile strength, strain recovery, hysteresis, compressive strength and degradation of CHCs of different composition. Subsequently, seamless and stable hybrid constructs consisting of PDSII® USP 2-0 CHCs embedded in porous collagen type I were produced. Compared to collagen alone, this hybrid showed superior strain recovery (93.5±0.9% vs 71.1±12.6% in longitudinal direction; 87.1±6.6% vs 57.2±4.6% in circumferential direction) and hysteresis (18.9±2.7% vs 51.1±12.0% in longitudinal direction; 11.5±4.6% vs 46.3±6.3% in circumferential direction). Furthermore, this hybrid construct showed an improved Young's modulus in both longitudinal (0.5±0.1MPavs 0.2±0.1MPa; 2.5-fold) and circumferential (1.65±0.07MPavs (2.9±0.3)×10 -2 MPa; 57-fold) direction, respectively, compared to templates created from collagen alone. Moreover, hybrid template characteristics could be modified by changing the CHC composition and CHCs were produced showing a mechanical behavior similar to the native ureter. CHC-enforced templates, which are easily tunable to meet different demands may be promising for tubular tissue engineering. Most tubular constructs lack sufficient strength and tunability to comply with the mechanical demands of native tissues. Therefore, we embedded coupled helical coils (CHCs) produced from biodegradable polymers - to

  7. [Construction and characterization of a cDNA library from human liver tissue of cirrhosis].

    Science.gov (United States)

    Chen, Xiao-hong; Chen, Zhi; Chen, Feng; Zhu, Hai-hong; Zhou, Hong-juan; Yao, Hang-ping

    2005-03-01

    To construct a cDNA library from human liver tissue of cirrhosis. The total RNA from human liver tissue of cirrhosis was extracted using Trizol method, and the mRNA was purified using mRNA purification kit. SMART technique and CDSIII/3' primer were used for first-strand cDNA synthesis. Long distance PCR was then used to synthesize the double-strand cDNA that was then digested by proteinase K and Sfi I, and was fractionated by CHOMA SPIN-400 column. The cDNA fragments longer than 0.4 kb were collected and ligated to lambdaTripl Ex2 vector. Then lambda-phage packaging reaction and library amplification were performed. The qualities of both unamplified and amplified cDNA libraries was strictly checked by conventional titer determination. Eleven plaques were randomly picked and tested using PCR with universal primers derived from the sequence flanking the vector. The titers of unamplifed and amplified libraries were 1.03 x 10(6) pfu/ml and 1.36 x 10(9) pfu/ml respectively. The percentages of recombinants from both libraries were 97.24 % in unamplified library and 99.02 % in amplified library. The lengths of the inserts were 1.02 kb in average (36.36 % 1 approximately equals 2 kb and 63.64 % 0.5 approximately equals 1.0 kb). A high quality cDNA library from human liver tissue of cirrhosis was constructed successfully, which can be used for screening and cloning new special genes associated with the occurrence of cirrhosis.

  8. Mesoderm Lineage 3D Tissue Constructs Are Produced at Large-Scale in a 3D Stem Cell Bioprocess.

    Science.gov (United States)

    Cha, Jae Min; Mantalaris, Athanasios; Jung, Sunyoung; Ji, Yurim; Bang, Oh Young; Bae, Hojae

    2017-09-01

    Various studies have presented different approaches to direct pluripotent stem cell differentiation such as applying defined sets of exogenous biochemical signals and genetic/epigenetic modifications. Although differentiation to target lineages can be successfully regulated, such conventional methods are often complicated, laborious, and not cost-effective to be employed to the large-scale production of 3D stem cell-based tissue constructs. A 3D-culture platform that could realize the large-scale production of mesoderm lineage tissue constructs from embryonic stem cells (ESCs) is developed. ESCs are cultured using our previously established 3D-bioprocess platform which is amenable to mass-production of 3D ESC-based tissue constructs. Hepatocarcinoma cell line conditioned medium is introduced to the large-scale 3D culture to provide a specific biomolecular microenvironment to mimic in vivo mesoderm formation process. After 5 days of spontaneous differentiation period, the resulting 3D tissue constructs are composed of multipotent mesodermal progenitor cells verified by gene and molecular expression profiles. Subsequently the optimal time points to trigger terminal differentiation towards cardiomyogenesis or osteogenesis from the mesodermal tissue constructs is found. A simple and affordable 3D ESC-bioprocess that can reach the scalable production of mesoderm origin tissues with significantly improved correspondent tissue properties is demonstrated. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Regeneration of the skin and muscle tissue in rainbow trout (Oncorhynchus mykiss) following mechanical injury

    DEFF Research Database (Denmark)

    Ingerslev, Hans-Christian; Nielsen, Michael Engelbrecht

    Mechanical injury induced by needles penetrating the skin and underlying muscle tissue in rainbow trout (Oncorhynchus mykiss) was used as a model to study the initial phase(s) of tissue regeneration. Tissue regeneration in humans is characterised by four phases; hemostatis, inflammation, prolifer......Mechanical injury induced by needles penetrating the skin and underlying muscle tissue in rainbow trout (Oncorhynchus mykiss) was used as a model to study the initial phase(s) of tissue regeneration. Tissue regeneration in humans is characterised by four phases; hemostatis, inflammation...

  10. Investigations of construction materials by means of cracking mechanics

    International Nuclear Information System (INIS)

    Bilous, W.; Wasiak, J.

    1995-01-01

    The diagnostic procedure for typical construction materials based on cracking tests has been presented. Results of investigations for aluminium base alloys and tungsten sintered materials have been shown and discussed. Application of the method for pipelines testing has been also performed. 6 figs, 2 tabs

  11. Mechanisms of inflammatory responses in obese adipose tissue

    NARCIS (Netherlands)

    Sun, S.Y.; Yewei, Ji; Kersten, A.H.; Qi, L.

    2012-01-01

    The fields of immunology and metabolism are rapidly converging on adipose tissue. During obesity, many immune cells infiltrate or populate in adipose tissue and promote a low-grade chronic inflammation. Studies to date have suggested that perturbation of inflammation is critically linked to nutrient

  12. Non-Fourier based thermal-mechanical tissue damage prediction for thermal ablation.

    Science.gov (United States)

    Li, Xin; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

    2017-01-02

    Prediction of tissue damage under thermal loads plays important role for thermal ablation planning. A new methodology is presented in this paper by combing non-Fourier bio-heat transfer, constitutive elastic mechanics as well as non-rigid motion of dynamics to predict and analyze thermal distribution, thermal-induced mechanical deformation and thermal-mechanical damage of soft tissues under thermal loads. Simulations and comparison analysis demonstrate that the proposed methodology based on the non-Fourier bio-heat transfer can account for the thermal-induced mechanical behaviors of soft tissues and predict tissue thermal damage more accurately than classical Fourier bio-heat transfer based model.

  13. DISPUTE RESOLUTION MECHANISM IN COMMERCIAL CONSTRUCTION PROJECTS: A REVIEW

    OpenAIRE

    Priyanka Sakate*, Dr.Arun W. Dhawale

    2017-01-01

    The number and complexity of contract disputes have increased dramatically in recent years. At the same time, the delays and costs associated with litigation have become more significant. This section provides an overview of dispute resolution methods commonly used. The increasing trend to alternative methods of resolving disputes suggests a considerable dissatisfaction with the traditional litigation process, at least in certain types of construction cases. However, it must be emphasized tha...

  14. PROSPECTS OF APPLICATION OF TISSUE-ENGINEERED PANCREATIC CONSTRUCTS IN THE TREATMENT OF TYPE 1 DIABETES

    Directory of Open Access Journals (Sweden)

    G. N. Skaletskaya

    2016-01-01

    Full Text Available Allotransplantation of pancreatic islets remains the most effective method of treatment of diabetes mellitus type 1 being capable under combination of favorable conditions (suffi cient number of isolated islets, effective combination of immunosuppressive drugs to reach the recipients’ insulin independence for several years. However, the overwhelming shortage of donor pancreas and limited post-transplantation islet survival do not allow increasing the number of such transplants and their effectiveness. This review presents a critical analysis of the work done by Russian and foreign authors onto creation of tissue-engineered pancreatic constructs that may lead to the resolution of the three main pancreatic islet transplantation issues: 1 lack of donor material; 2 necessity of immunosuppressive therapy; 3 limited survival and functional activity of the islet.

  15. Electro-mechanical dynamics of spiral waves in a discrete 2D model of human atrial tissue.

    Directory of Open Access Journals (Sweden)

    Paul Brocklehurst

    Full Text Available We investigate the effect of mechano-electrical feedback and atrial fibrillation induced electrical remodelling (AFER of cellular ion channel properties on the dynamics of spiral waves in a discrete 2D model of human atrial tissue. The tissue electro-mechanics are modelled using the discrete element method (DEM. Millions of bonded DEM particles form a network of coupled atrial cells representing 2D cardiac tissue, allowing simulations of the dynamic behaviour of electrical excitation waves and mechanical contraction in the tissue. In the tissue model, each cell is modelled by nine particles, accounting for the features of individual cellular geometry; and discrete inter-cellular spatial arrangement of cells is also considered. The electro-mechanical model of a human atrial single-cell was constructed by strongly coupling the electrophysiological model of Colman et al. to the mechanical myofilament model of Rice et al., with parameters modified based on experimental data. A stretch-activated channel was incorporated into the model to simulate the mechano-electrical feedback. In order to investigate the effect of mechano-electrical feedback on the dynamics of spiral waves, simulations of spiral waves were conducted in both the electromechanical model and the electrical-only model in normal and AFER conditions, to allow direct comparison of the results between the models. Dynamics of spiral waves were characterized by tracing their tip trajectories, stability, excitation frequencies and meandering range of tip trajectories. It was shown that the developed DEM method provides a stable and efficient model of human atrial tissue with considerations of the intrinsically discrete and anisotropic properties of the atrial tissue, which are challenges to handle in traditional continuum mechanics models. This study provides mechanistic insights into the complex behaviours of spiral waves and the genesis of atrial fibrillation by showing an important role of

  16. A nano-sandwich construct built with graphene nanosheets and carbon nanotubes enhances mechanical properties of hydroxyapatite-polyetheretherketone scaffolds.

    Science.gov (United States)

    Feng, Pei; Peng, Shuping; Wu, Ping; Gao, Chengde; Huang, Wei; Deng, Youwen; Xiao, Tao; Shuai, Cijun

    2016-01-01

    A nano-sandwich construct was built by combining two-dimensional graphene nanosheets (GNSs) and one-dimensional carbon nanotubes (CNTs) to improve the mechanical properties of hydroxyapatite-polyetheretherketone (HAP-PEEK) scaffolds for bone tissue engineering. In this nano-sandwich construct, the long tubular CNTs penetrated the interlayers of graphene and prevented their aggregation, increasing the effective contact area between the construct and matrix. The combination of GNSs and CNTs in a weight ratio of 2:8 facilitated the dispersion of each other and provided a synergetic effect in enhancing the mechanical properties. The compressive strength and modulus of the scaffolds were increased by 63.58% and 56.54% at this time compared with those of HAP-PEEK scaffolds, respectively. The carbon-based fillers, pulling out and bridging, were also clearly observed in the matrix. Moreover, the dangling of CNTs and their entangling with GNSs further reinforced the mechanical properties. Furthermore, apatite layer formed on the scaffold surface after immersing in simulated body fluid, and the cells attached and spread well on the surface of the scaffolds and displayed good viability, proliferation, and differentiation. These evidence indicate that the HAP-PEEK scaffolds enhanced by GNSs and CNTs are a promising alternative for bone tissue engineering.

  17. Investigation of the in vitro culture process for skeletal-tissue-engineered constructs using computational fluid dynamics and experimental methods.

    Science.gov (United States)

    Hossain, Md Shakhawath; Chen, X B; Bergstrom, D J

    2012-12-01

    The in vitro culture process via bioreactors is critical to create tissue-engineered constructs (TECs) to repair or replace the damaged tissues/organs in various engineered applications. In the past, the TEC culture process was typically treated as a black box and performed on the basis of trial and error. Recently, computational fluid dynamics (CFD) has demonstrated its potential to analyze the fluid flow inside and around the TECs, therefore, being able to provide insight into the culture process, such as information on the velocity field and shear stress distribution that can significantly affect such cellular activities as cell viability and proliferation during the culture process. This paper briefly reviews the CFD and experimental methods used to investigate the in vitro culture process of skeletal-type TECs in bioreactors, where mechanical deformation of the TEC can be ignored. Specifically, this paper presents CFD modeling approaches for the analysis of the velocity and shear stress fields, mass transfer, and cell growth during the culture process and also describes various particle image velocimetry (PIV) based experimental methods to measure the velocity and shear stress in the in vitro culture process. Some key issues and challenges are also identified and discussed along with recommendations for future research.

  18. Confocal fluorometer for diffusion tracking in 3D engineered tissue constructs

    Science.gov (United States)

    Daly, D.; Zilioli, A.; Tan, N.; Buttenschoen, K.; Chikkanna, B.; Reynolds, J.; Marsden, B.; Hughes, C.

    2016-03-01

    We present results of the development of a non-contacting instrument, called fScan, based on scanning confocal fluorometry for assessing the diffusion of materials through a tissue matrix. There are many areas in healthcare diagnostics and screening where it is now widely accepted that the need for new quantitative monitoring technologies is a major pinch point in patient diagnostics and in vitro testing. With the increasing need to interpret 3D responses this commonly involves the need to track the diffusion of compounds, pharma-active species and cells through a 3D matrix of tissue. Methods are available but to support the advances that are currently only promised, this monitoring needs to be real-time, non-invasive, and economical. At the moment commercial meters tend to be invasive and usually require a sample of the medium to be removed and processed prior to testing. This methodology clearly has a number of significant disadvantages. fScan combines a fiber based optical arrangement with a compact, free space optical front end that has been integrated so that the sample's diffusion can be measured without interference. This architecture is particularly important due to the "wet" nature of the samples. fScan is designed to measure constructs located within standard well plates and a 2-D motion stage locates the required sample with respect to the measurement system. Results are presented that show how the meter has been used to evaluate movements of samples through collagen constructs in situ without disturbing their kinetic characteristics. These kinetics were little understood prior to these measurements.

  19. [Construction of a cDNA library from liver tissue of rhesus monkey, Macaca mulatta].

    Science.gov (United States)

    Qin, Sheng-fang; Tan, Wei-dong; Chen, You-nan; Ding, Yang; Li, Sheng-fu; Li, Hong-xia; Wang, Li; Yang, Rong; Lu, Yan-rong

    2007-06-01

    To screen the target rhesus genes and give some basic genetic evidences to its value as one of the most important animal model in biomedical study, we constructed a cDNA expression library from liver tissue of a healthy rhesus monkey. With Trizol reagent, the total RNA was extracted from healthy rhesus liver tissue. By mutant Moloney Murine Leukemia Virus Reverse Transcriptase (MMLV-RT), the first-strand cDNA was synthesized from purified mRNA, and subsequently the second-strand cDNA was generated via E. coli DNA polymerase I . Then, the EcoR I adapter was added to the synthesized double-strand cDNA, which was subsequently digested by Xho I restriction enzyme and fractionated with CHROMA APIN-400 column. The fractionated cDNA fragments to be longer than 0. 5 kb were ligated into lambda ZAP express vector to form the phagemid cDNA recombinants, which were further packaged into the lambda ZAP cDNA library according to the standard protocol with phage lambda Gold packaging extract. In order to get more stable clones with larger quantity, the primary library was amplified through infecting the host strain XL1-Blue MRF'. Then, the library titre, recombinant rate and length of inserted cDNA were measured, respectively. The capacity of the primary stand or unamplified library was 1. 2X 10(6) pfu. The titers of the unamplified library or the amplified library was 1.1 X 10(6) mixture, pfu/mL or 7. 7 X 10(9) pfu/mL respectively, the percentages of recombinants were 99. 3% and 98. 2%, and the average lengths of the inserts were 2.0 kb and 2. 3 kb, respectively. An excellent cDNA expression library has been constructed successfully, which would lay solid foundation for transplantation study and pre-clinic evaluation of related drugs.

  20. Mineralization Induction of Gingival Fibroblasts and Construction of a Sandwich Tissue-Engineered Complex for Repairing Periodontal Defects.

    Science.gov (United States)

    Wu, Mingxuan; Wang, Jie; Zhang, Yanning; Liu, Huijuan; Dong, Fusheng

    2018-02-22

    BACKGROUND The ideal healing technique for periodontal tissue defects would involve the functional regeneration of the alveolar bone, cementum, and periodontal ligament, with new periodontal attachment formation. In this study, gingival fibroblasts were induced and a "sandwich" tissue-engineered complex (a tissue-engineered periodontal membrane between 2 tissue-engineered mineralized membranes) was constructed to repair periodontal defects. We evaluated the effects of gingival fibroblasts used as seed cells on the repair of periodontal defects and periodontal regeneration. MATERIAL AND METHODS Primitively cultured gingival fibroblasts were seeded bilaterally on Bio-Gide collagen membrane (a tissue-engineered periodontal membrane) or unilaterally on small intestinal submucosa segments, and their mineralization was induced. A tissue-engineered sandwich was constructed, comprising the tissue-engineered periodontal membrane flanked by 2 mineralized membranes. Periodontal defects in premolar regions of Beagles were repaired using the tissue-engineered sandwich or periodontal membranes. Periodontal reconstruction was compared to normal and trauma controls 10 or 20 days postoperatively. RESULTS Periodontal defects were completely repaired by the sandwich tissue-engineered complex, with intact new alveolar bone and cementum, and a new periodontal ligament, 10 days postoperatively. CONCLUSIONS The sandwich tissue-engineered complex can achieve ideal periodontal reconstruction rapidly.

  1. [Construction of forward and reverse subtracted cDNA libraries between muscle tissue of Meishan and Landrace pigs].

    Science.gov (United States)

    Xu, De-Quan; Zhang, Yi-Bing; Xiong, Yuan-Zhu; Gui, Jian-Fang; Jiang, Si-Wen; Su, Yu-Hong

    2003-07-01

    Using suppression subtractive hybridization (SSH) technique, forward and reverse subtracted cDNA libraries were constructed between Longissimus muscles from Meishan and Landrace pigs. A housekeeping gene, G3PDH, was used to estimate the efficiency of subtractive cDNA. In two cDNA libraries, G3PDH was subtracted very efficiently at appropriate 2(10) and 2(5) folds, respectively, indicating that some differentially expressed genes were also enriched at the same folds and the two subtractive cDNA libraries were very successful. A total of 709 and 673 positive clones were isolated from forward and reverse subtracted cDNA libraries, respectively. Analysis of PCR showed that most of all plasmids in the clones contained 150-750 bp inserts. The construction of subtractive cDNA libraries between muscle tissue from different pig breeds laid solid foundations for isolating and identifying the genes determining muscle growth and meat quality, which will be important to understand the mechanism of muscle growth, determination of meat quality and practice of molecular breeding.

  2. Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering

    International Nuclear Information System (INIS)

    Mirahmadi, Fereshteh; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali; Bonakdar, Shahin

    2013-01-01

    Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber–hydrogel composite for GAG content and in two-layer electrospun fiber–hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. - Highlights: • Chitosan hydrogel composites fabricated by two forms of silk fiber • Silk fibers provide structural support for the hydrogel matrix. • The mechanical properties of hydrogel significantly improved by associating with silk. • Production of GAG and collagen type II was demonstrated within the scaffolds

  3. Construction of tissue-engineered heart valves by using decellularized scaffolds and endothelial progenitor cells.

    Science.gov (United States)

    Fang, Ning-Tao; Xie, Shang-Zhe; Wang, Song-Mei; Gao, Hong-Yang; Wu, Chun-Gen; Pan, Luan-Feng

    2007-04-20

    . Platelets adhesion experiments suggested that the neo-endothelium was non-thrombogenic. The expression levels of eNOS and t-PA genes in the neo-endothelium were quite similar to those in human umbilical vein endothelial cells. EPCs isolated from the human umbilical cord blood can differentiate into endothelial cells in vitro and form a functional endothelium atop decellularized heart valve scaffolds. Thus, EPCs may be a promising cell source for constructing tissue-engineered heart valves.

  4. [Construction of a subtracted cDNA library of differentially expressed genes in human normal liver tissue and primary hepatocellular carcinoma tissue].

    Science.gov (United States)

    Li, J; Xu, X; Han, B; Huang, G; Qian, G; Liang, P; Yang, T

    2001-12-01

    To construct a subtracted cDNA library of differentially expressed genes in human normal liver tissue and primary hepatocellular carcinoma (HCC) tissue. Using the suppression subtractive hybridization (SSH), a novel technique has been described recently. cDNA fragments of missing or low expressing tumor suppressor genes in HCC tissue were isolated using paracancerous normal liver tissue and HCC tissue as targets. Then these cDNA fragments were directly inserted into T/A cloning vector to set up the subtractive library. Amplification of the library was carried out with transformation of E.coli by high voltage electroperforation. One hundred positive bacteria clones were randomly picked and identified using enzyme restriction method. The amplified library contained more than 4,000 positive bacteria clones. Random analysis of 100 clones with enzyme restriction method showed that all clones contained 200-600 bp inserts. A subtracted cDNA library of differentially expressed genes in human normal liver tissue and HCC tissue is constructed successfully with SSH and T/A cloning techniques. The library is efficient and lays solid foundation for screening and cloning new and specific missing or low expressing tumor suppressor genes of HCC.

  5. Insertion mechanics of bioinspired needles into soft tissues.

    Science.gov (United States)

    Sahlabadi, Mohammad; Khodaei, Seyedvahid; Jezler, Kyle; Hutapea, Parsaoran

    2017-12-22

    Most studies to date confirm that any increase in the needle insertion force increases the damage to the tissue. When it comes to brain tissue, even minor damage can cause a long-lasting traumatic brain injury. Thus there is a great demand for innovative minimally invasive needles among the medical community. In our previous studies a novel bioinspired needle design with specially designed barbs was used to perform insertion tests into Polyvinyl chloride (PVC) tissue-mimicking gels, in which it decreased the insertion force by as much as 25%. In this work, bioinspired needles were designed using a CAD software, and were then manufactured using a 3 D printer. The insertion tests into bovine brain and liver were then performed to further investigate the performance of our bioinspired needles in real tissues. Our results show that there was a 10-25% decrease in the insertion force for insertions into bovine brain, and a 35-45% reduction in the insertion force for insertions into bovine liver using the proposed bioinspired needles. The reduction in the insertion force is due to the decrease in the friction force of the bioinspired needle with the bovine tissues, and its results are consistent with our previous results.

  6. Mechanism of state regulation of innovation development of the construction sphere

    Directory of Open Access Journals (Sweden)

    Semenov Vasil F.

    2014-01-01

    Full Text Available The article provides theoretical and methodological justification of the process of formation of the mechanism of state regulation of innovation development of the construction sphere of Ukraine. The article studies conceptual provisions of formation of the mechanism of state regulation of innovation development of the construction sphere. It develops the mechanism of state regulation of innovation development of the construction sphere, realisation of which would ensure stable, effective and system functioning of the construction sphere on the basis of newest technologies and would become a powerful incentive for the national economy development. It analyses main principles, functions and instruments of state regulation of innovation development of the construction sphere in detail. It offers and justifies organisational, information, personnel and financial and economic support and also tax stimulation of creation of the mechanism of state regulation of innovation development of the construction sphere. Prospects of further studies in this direction is identification of priorities of innovation development of construction in the regional context, development of directions of improvement of the mechanism of state regulation of innovation development of the construction sphere and assessment of efficiency of the state impact on innovation development of construction.

  7. Development of volume-stable adipose tissue constructs using polycaprolactone-based polyurethane scaffolds and fibrin hydrogels.

    Science.gov (United States)

    Wittmann, Katharina; Storck, Katharina; Muhr, Christian; Mayer, Helena; Regn, Sybille; Staudenmaier, Rainer; Wiese, Hinrich; Maier, Gerhard; Bauer-Kreisel, Petra; Blunk, Torsten

    2016-10-01

    Adipose tissue engineering aims at the restoration of soft tissue defects and the correction of contour deformities. It is therefore crucial to provide functional adipose tissue implants with appropriate volume stability. Here, we investigate two different fibrin formulations, alone or in combination with biodegradable polyurethane (PU) scaffolds as additional support structures, with regard to their suitability to generate volume-stable adipose tissue constructs. Human adipose-derived stem cells (ASCs) were incorporated in a commercially available fibrin sealant as well as a stable fibrin hydrogel previously developed by our group. The composite constructs made from the commercially available fibrin and porous poly(ε-caprolactone)-based polyurethane scaffolds exhibited increased volume stability as compared to fibrin gels alone; however, only constructs using the stable fibrin gels completely maintained their size and weight for 21 days. Adipogenesis of ASCs was not impaired by the additional PU scaffold. After induction with a common hormonal cocktail, for constructs with either fibrin formulation, strong adipogenic differentiation of ASCs was observed after 21 days in vitro. Furthermore, upregulation of adipogenic marker genes was demonstrated at mRNA (PPARγ, C/EBPα, GLUT4 and aP2; qRT-PCR) and protein (leptin; ELISA) levels. Stable fibrin/PU constructs were further evaluated in a pilot in vivo study, resulting in areas of well-vascularized adipose tissue within the implants after only 5 weeks. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Multifactorial Optimization of Contrast-Enhanced Nanofocus Computed Tomography for Quantitative Analysis of Neo-Tissue Formation in Tissue Engineering Constructs

    Science.gov (United States)

    Sonnaert, Maarten; Kerckhofs, Greet; Papantoniou, Ioannis; Van Vlierberghe, Sandra; Boterberg, Veerle; Dubruel, Peter; Luyten, Frank P.; Schrooten, Jan; Geris, Liesbet

    2015-01-01

    To progress the fields of tissue engineering (TE) and regenerative medicine, development of quantitative methods for non-invasive three dimensional characterization of engineered constructs (i.e. cells/tissue combined with scaffolds) becomes essential. In this study, we have defined the most optimal staining conditions for contrast-enhanced nanofocus computed tomography for three dimensional visualization and quantitative analysis of in vitro engineered neo-tissue (i.e. extracellular matrix containing cells) in perfusion bioreactor-developed Ti6Al4V constructs. A fractional factorial ‘design of experiments’ approach was used to elucidate the influence of the staining time and concentration of two contrast agents (Hexabrix and phosphotungstic acid) and the neo-tissue volume on the image contrast and dataset quality. Additionally, the neo-tissue shrinkage that was induced by phosphotungstic acid staining was quantified to determine the operating window within which this contrast agent can be accurately applied. For Hexabrix the staining concentration was the main parameter influencing image contrast and dataset quality. Using phosphotungstic acid the staining concentration had a significant influence on the image contrast while both staining concentration and neo-tissue volume had an influence on the dataset quality. The use of high concentrations of phosphotungstic acid did however introduce significant shrinkage of the neo-tissue indicating that, despite sub-optimal image contrast, low concentrations of this staining agent should be used to enable quantitative analysis. To conclude, design of experiments allowed us to define the most optimal staining conditions for contrast-enhanced nanofocus computed tomography to be used as a routine screening tool of neo-tissue formation in Ti6Al4V constructs, transforming it into a robust three dimensional quality control methodology. PMID:26076131

  9. Depth-Resolved Mapping of Tissue Mechanical Properties Using a Novel Optical Approach

    OpenAIRE

    Hajjarian, Zeinab; Nadkarni, Seemantni K.

    2011-01-01

    Progression of most diseases, such as atherosclerosis, cancer, neurodegenerative disease and osteoarthritis is accompanied with drastic changes in biomechanics of tissue. Hence, non-contact and non-invasive technologies for 3-dimensional mapping of tissue biomechanics are invaluable for diagnostic purposes. Laser speckle Microrheology (LSM) is developed in our lab to enable high resolution mechanical evaluation of tissue. To this end, the tissue sample is illuminated by a coherent and focused...

  10. [Construction and evaluation of the tissue engineered nerve of bFGF-PLGA sustained release microspheres].

    Science.gov (United States)

    Wang, Guanglin; Lin, Wei; Gao, Weiqiang; Xiao, Yuhua; Dong, Changchao

    2008-12-01

    To study the outcomes of nerve defect repair with the tissue engineered nerve, which is composed of the complex of SCs, 30% ECM gel, bFGF-PLGA sustained release microspheres, PLGA microfilaments and permeable poly (D, L-lactic acid) (PDLLA) catheters. SCs were cultured and purified from the sciatic nerves of 1-day-old neonatal SD rats. The 1st passage cells were compounded with bFGF-PLGA sustained release microspheres and ECM gel, and then were injected into permeable PDLLA catheters with PLGA microfilaments inside. In this way, the tissue engineered nerve was constructed. Sixty SD rats were included. The model of 15-mm sciatic nerve defects was made, and then the rats were randomly divided into 5 groups, with 12 rats in each. In group A, autograft was adopted. In group B, the blank PDLLA catheters with PBS inside were used. In group C, PDLLA catheters, with PLGA microfilaments and 30% ECM gel inside, were used. In group D, PDLLA catheters, with PLGA microfilaments, SCs and 30% ECM gel inside, were used. In group E, the tissue engineered nerve was applied. After the operation, observation was made for general conditions of the rats. The sciatic function index (SFI) analysis was performed at 12, 16, 20 and 24 weeks after the operation, respectively. Electrophysiological detection and histological observation were performed at 12 and 24 weeks after the operation, respectively. All rats survived to the end of the experiment. At 12 and 16 weeks after the operation, group E was significantly different from group B in SFI (P fibers in group E were significantly differents from those in groups A, B and C (P fibers in group E were smaller than those in group A (P fibers in group E was significantly different from those in groups A, B, C (P fibers in group E were bigger than those in groups B and C (P < 0.05). The tissue engineered nerve with the complex of SCs, ECM gel, bFGF-PLGA sustained release microspheres, PLGA microfilaments and permeable PDLLA catheters promote

  11. Mechanical cues in orofacial tissue engineering and regenerative medicine

    NARCIS (Netherlands)

    Brouwer, K.M.; Lundvig, D.M.S.; Middelkoop, E.; Wagener, F.A.D.T.G.; Hoff, J.W. Von den

    2015-01-01

    Cleft lip and palate patients suffer from functional, aesthetical, and psychosocial problems due to suboptimal regeneration of skin, mucosa, and skeletal muscle after restorative cleft surgery. The field of tissue engineering and regenerative medicine (TE/RM) aims to restore the normal physiology of

  12. Let's push things forward: disruptive technologies and the mechanics of tissue assembly.

    Science.gov (United States)

    Varner, Victor D; Nelson, Celeste M

    2013-09-01

    Although many of the molecular mechanisms that regulate tissue assembly in the embryo have been delineated, the physical forces that couple these mechanisms to actual changes in tissue form remain unclear. Qualitative studies suggest that mechanical loads play a regulatory role in development, but clear quantitative evidence has been lacking. This is partly owing to the complex nature of these problems - embryonic tissues typically undergo large deformations and exhibit evolving, highly viscoelastic material properties. Still, despite these challenges, new disruptive technologies are enabling study of the mechanics of tissue assembly in unprecedented detail. Here, we present novel experimental techniques that enable the study of each component of these physical problems: kinematics, forces, and constitutive properties. Specifically, we detail advances in light sheet microscopy, optical coherence tomography, traction force microscopy, fluorescence force spectroscopy, microrheology and micropatterning. Taken together, these technologies are helping elucidate a more quantitative understanding of the mechanics of tissue assembly.

  13. Thermal-mechanical deformation modelling of soft tissues for thermal ablation.

    Science.gov (United States)

    Li, Xin; Zhong, Yongmin; Jazar, Reza; Subic, Aleksandar

    2014-01-01

    Modeling of thermal-induced mechanical behaviors of soft tissues is of great importance for thermal ablation. This paper presents a method by integrating the heating process with thermal-induced mechanical deformations of soft tissues for simulation and analysis of the thermal ablation process. This method combines bio-heat transfer theories, constitutive elastic material law under thermal loads as well as non-rigid motion dynamics to predict and analyze thermal-mechanical deformations of soft tissues. The 3D governing equations of thermal-mechanical soft tissue deformation are discretized by using the finite difference scheme and are subsequently solved by numerical algorithms. Experimental results show that the proposed method can effectively predict the thermal-induced mechanical behaviors of soft tissues, and can be used for the thermal ablation therapy to effectively control the delivered heat energy for cancer treatment.

  14. In vitro tendon tissue development from human fibroblasts demonstrates collagen fibril diameter growth associated with a rise in mechanical strength.

    Science.gov (United States)

    Herchenhan, Andreas; Bayer, Monika L; Svensson, René B; Magnusson, S Peter; Kjaer, Michael

    2013-01-01

    Collagen-rich tendons and ligaments are important for joint stability and force transmission, but the capacity to form new tendon is poorly understood. In the present study, we investigated mechanical strength, fibril size, and structure during development of tendon-like tissue from adult human tenocytes (termed tendon constructs) in vitro over 5 weeks in 3D tissue culture. The constructs displayed large elongated tendon cells aligned along the tendon axis together with collagen fibrils that increased in diameter by 50% from day 14 to 35, which approaches that observed in adult human tendon in vivo. The increase in diameter was accompanied by a 5-fold increase in mechanical strength (0.9±0.1 MPa to 4.9±0.6 MPa) and Young's modulus (5.8±0.9 MPa to 32.3±4.2 MPa), while the maximal strain at failure (16%) remained constant throughout the 5-week culture period. The present study demonstrates that 3D tendon constructs can be formed by isolated human tendon fibroblasts, and when these constructs are subjected to static self-generated tension, the fibrils will grow in size and strength approaching that of adult human tendon in vivo. Copyright © 2012 Wiley Periodicals, Inc.

  15. PACING DEVICE FOR SWIMMING. MECHANICAL CONSTRUCTION OF CONSTANT SPEED

    Directory of Open Access Journals (Sweden)

    MESSINIS S.

    2010-04-01

    Full Text Available The pace in swimming is very important because it allows swimmers to allocate their forces accordingly, and therefore a distance to travel as quickly as possible. The training pace at different swimmingspeeds and combinations thereof, is an important part of training before the competitions.The definition and maintenance of the stable and swimmer specific speed is difficult to achieve and requires considerable effort and experience. To determine the desired rate of accuracy by the researchers and their coaches used till now, various audio and visual media.However, some of these institutions did not very accurately measure the rate and not all styles of swimming, while other aspects affect the proper swimming. In this construction, a key objective is to solve the problems occurring in the previous constructions, the modern technological development of them and the adaption of the specificities of different swimming styles.This device consists of an electro 3 / 8 of the horse, a flange, a single inverter from 3 / 8 to ½ of the horse, pulleys with taper Bush, flange axle, pulleys, platforms and a 52 meters cable. The assembly and operation is as follows: At the edge of the pool next to the platform is placed the base of pulleys, the electro setis connected to the inverter and the axle flange.Precisely opposite is positioned the other base. Along the pool «moves» the cable that connects the two bases, located 150 cm above the water. A fixed point on the cable is marked with paint in order to be visible to the swimmer during backstroke swimming while for other styles we adapt a lamination at the cable vertically inthe pool, above the surface a sheet of 15 cm which is painted with strong color that is visible from the athlete and will precede him. Setting the speed with inverter it starts from one end of the tank leading to the other, doing a circular motion.The swimmer is required to follow the marked point of the cable in the backstroke or

  16. BIOCHEMICAL MECHANISM OF AUTOLYTIC PROCESSES OF MUSCULAR TISSUE OF FISHES

    Directory of Open Access Journals (Sweden)

    L. V. Antipova

    2015-01-01

    Full Text Available The conducted researches allowed to establish that intensive disintegration of a muscular glycogen leads to sharp decrease in size рН muscular tissue in the sour party that in turn affects a chemical composition and physic-colloidal structure of proteins therefore: resistance of meat of fish to action of putrefactive microorganisms increases; solubility of muscle proteins, level of their hydration which is water connecting abilities decreases; there is a swelling of collagen of connecting fabric; activity of the cathepsin (an optimum рН 5,3 causing hydrolysis of proteins at later stages of an autolysis increases; the bicarbonate system of muscular tissue with release of carbon dioxide collapses; predecessors of taste and aroma of meat are formed; process of oxidation of lipids becomes more active. As a result of accumulation dairy, phosphoric and other acids in meat of fish concentration of hydrogen ions of that decrease рН is result increases. Sharply shown sour environment and availability of inorganic phosphorus is considered the reason of disintegration of an actin-myosin complex on actin and a myosin which begins after 8 hours of storage, i.e. there comes the period of relaxation of muscle fibers and the period of permission of an numbness, and then the last stage of maturing of meat – deep autolysis. Thus, on the basis of classical ideas of biochemical changes of meat of land animals and summarizing the obtained data on posthumous changes in muscular tissue of fishes, it is possible to draw a conclusion that they have similar nature of regularity in comparison with muscular tissue of land animals, but their main difference is higher speed of course of autolytic transformations. It in turn leads to faster change of FTS of meat of fishes who are the defining indicators when developing assortment groups of products taking into account stages of an autolysis in meat.

  17. Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues

    OpenAIRE

    Yu, Hye-Sun; Kim, Jung-Ju; Kim, Hae-Won; Lewis, Mark P; Wall, Ivan

    2016-01-01

    Mechanical loading is recognized to play an important role in regulating the behaviors of cells in bone and surrounding tissues in vivo. Many in vitro studies have been conducted to determine the effects of mechanical loading on individual cell types of the tissues. In this review, we focus specifically on the use of the Flexercell system as a tool for studying cellular responses to mechanical stretch. We assess the li...

  18. Tissue mechanics, animal models, and pelvic organ prolapse: a review.

    Science.gov (United States)

    Abramowitch, Steven D; Feola, Andrew; Jallah, Zegbeh; Moalli, Pamela A

    2009-05-01

    Pelvic floor disorders such as pelvic organ prolapse, urinary incontinence, and fecal incontinence affect a large number of women each year. The pelvic floor can be thought of as a biomechanical structure due to the complex interaction between the vagina and its supportive structures that are designed to withstand the downward descent of the pelvic organs in response to increases in abdominal pressure. Although previous work has highlighted the biochemical changes that are associated with specific risk factors (i.e. parity, menopause, and genetics), little work has been done to understand the biomechanical changes that occur within the vagina and its supportive structures to prevent the onset of these pelvic floor disorders. Human studies are often limited due to the challenges of obtaining large tissue samples and ethical concerns. Therefore, it is necessary to investigate the use of animal models and their importance in understanding how different risk factors affect the biomechanical properties of the vagina and its supportive structures. In this review paper, we will discuss the different animal models that have been previously used to characterize the biomechanical properties of the vagina: including non-human primates, rodents, rabbits, and sheep. The anatomy and preliminary biomechanical findings are discussed along with the importance of considering experimental conditions, tissue anisotropy, and viscoelasticity when characterizing the biomechanical properties of vaginal tissue. Although there is not a lot of biomechanics research related to the vagina and pelvic floor, the future is exciting due to the significant potential for scientific findings that will improve our understanding of these conditions and hopefully lead to improvements in the prevention and treatment of pelvic disorders.

  19. Tissue microarray design and construction for scientific, industrial and diagnostic use

    Science.gov (United States)

    Pilla, Daniela; Bosisio, Francesca M.; Marotta, Roberto; Faggi, Stefano; Forlani, Paolo; Falavigna, Maurizio; Biunno, Ida; Martella, Emanuele; De Blasio, Pasquale; Borghesi, Simone; Cattoretti, Giorgio

    2012-01-01

    Context: In 2013 the high throughput technology known as Tissue Micro Array (TMA) will be fifteen years old. Its elements (design, construction and analysis) are intuitive and the core histopathology technique is unsophisticated, which may be a reason why has eluded a rigorous scientific scrutiny. The source of errors, particularly in specimen identification and how to control for it is unreported. Formal validation of the accuracy of segmenting (also known as de-arraying) hundreds of samples, pairing with the sample data is lacking. Aims: We wanted to address these issues in order to bring the technique to recognized standards of quality in TMA use for research, diagnostics and industrial purposes. Results: We systematically addressed the sources of error and used barcode-driven data input throughout the whole process including matching the design with a TMA virtual image and segmenting that image back to individual cases, together with the associated data. In addition we demonstrate on mathematical grounds that a TMA design, when superimposed onto the corresponding whole slide image, validates on each and every sample the correspondence between the image and patient's data. Conclusions: High throughput use of the TMA technology is a safe and efficient method for research, diagnosis and industrial use if all sources of errors are identified and addressed. PMID:23372983

  20. Tissue microarray design and construction for scientific, industrial and diagnostic use

    Directory of Open Access Journals (Sweden)

    Daniela Pilla

    2012-01-01

    Full Text Available Context: In 2013 the high throughput technology known as Tissue Micro Array (TMA will be fifteen years old. Its elements (design, construction and analysis are intuitive and the core histopathology technique is unsophisticated, which may be a reason why has eluded a rigorous scientific scrutiny. The source of errors, particularly in specimen identification and how to control for it is unreported. Formal validation of the accuracy of segmenting (also known as de-arraying hundreds of samples, pairing with the sample data is lacking. Aims: We wanted to address these issues in order to bring the technique to recognized standards of quality in TMA use for research, diagnostics and industrial purposes. Results: We systematically addressed the sources of error and used barcode-driven data input throughout the whole process including matching the design with a TMA virtual image and segmenting that image back to individual cases, together with the associated data. In addition we demonstrate on mathematical grounds that a TMA design, when superimposed onto the corresponding whole slide image, validates on each and every sample the correspondence between the image and patient′s data. Conclusions: High throughput use of the TMA technology is a safe and efficient method for research, diagnosis and industrial use if all sources of errors are identified and addressed.

  1. Construction and characterization of an electrospun tubular scaffold for small-diameter tissue-engineered vascular grafts: a scaffold membrane approach.

    Science.gov (United States)

    Hu, Jin-Jia; Chao, Wei-Chih; Lee, Pei-Yuan; Huang, Chih-Hao

    2012-09-01

    Based on a postulate that the microstructure of a scaffold can influence that of the resulting tissue and hence its mechanical behavior, we fabricated a small-diameter tubular scaffold (∼3 mm inner diameter) that has a microstructure similar to the arterial media using a scaffold membrane approach. Scaffold membranes that contain randomly oriented, moderately aligned, or highly aligned fibers were fabricated by collecting electrospun poly([epsilon]-caprolactone) fibers on a grounded rotating drum at three different drum rotation speeds (250, 1000, and 1500 rpm). Membranes of each type were wrapped around a small-diameter mandrel to form the tubular scaffolds. Particularly, the tubular scaffolds with three different off-axis fiber angles (30, 45, and 60 degree) were formed using membranes that contain aligned fibers. These scaffolds were subjected to biaxial mechanical testing to examine the effects of fiber directions as well as the distribution of fiber orientations on their mechanical properties. The circumferential elastic modulus of the tubular scaffold was closely related to the fiber directions; the larger the off-axis fiber angle the greater the circumferential elastic modulus. The distribution of fiber orientations, on the other hand, manifested itself in the mechanical behavior via the Poisson effect. Similar to cell sheet-based vascular tissue engineering, tubular cell-seeded constructs were prepared by wrapping cell-seeded scaffold membranes, alleviating the difficulty associated with cell seeding in electrospun scaffolds. Histology of the construct illustrated that cells were aligned to the fiber directions in the construct, demonstrating the potential to control the microstructure of tissue-engineered vascular grafts using the electrospun scaffold membrane. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Cancer and Leukemia Group B Pathology Committee guidelines for tissue microarray construction representing multicenter prospective clinical trial tissues.

    Science.gov (United States)

    Rimm, David L; Nielsen, Torsten O; Jewell, Scott D; Rohrer, Daniel C; Broadwater, Gloria; Waldman, Frederic; Mitchell, Kisha A; Singh, Baljit; Tsongalis, Gregory J; Frankel, Wendy L; Magliocco, Anthony M; Lara, Jonathan F; Hsi, Eric D; Bleiweiss, Ira J; Badve, Sunil S; Chen, Beiyun; Ravdin, Peter M; Schilsky, Richard L; Thor, Ann; Berry, Donald A

    2011-06-01

    Practice-changing evidence requires confirmation, preferably in multi-institutional clinical trials. The collection of tissue within such trials has enabled biomarker studies and evaluation of companion diagnostic tests. Tissue microarrays (TMAs) have become a standard approach in many cooperative oncology groups. A principal goal is to maximize the number of assays with this precious tissue. However, production strategies for these arrays have not been standardized, possibly decreasing the value of the study. In this article, members of the Cancer and Leukemia Group B Pathology Committee relay our experiences as array facility directors and propose guidelines regarding the production of high-quality TMAs for cooperative group studies. We also discuss statistical issues arising from having a proportion of patients available for TMAs and the possibility that patients with TMAs fail to represent the greater study population.

  3. Mechanical phenotyping of cells and extracellular matrix as grade and stage markers of lung tumor tissues.

    Science.gov (United States)

    Panzetta, Valeria; Musella, Ida; Rapa, Ida; Volante, Marco; Netti, Paolo A; Fusco, Sabato

    2017-07-15

    The mechanical cross-talk between cells and the extra-cellular matrix (ECM) regulates the properties, functions and healthiness of the tissues. When this is disturbed it changes the mechanical state of the tissue components, singularly or together, and cancer, along with other diseases, may start and progress. However, the bi-univocal mechanical interplay between cells and the ECM is still not properly understood. In this study we show how a microrheology technique gives us the opportunity to evaluate the mechanics of cells and the ECM at the same time. The mechanical phenotyping was performed on the surgically removed tissues of 10 patients affected by adenocarcinoma of the lung. A correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Our findings suggest a sort of asymmetric modification of the mechanical properties of the cells and the extra-cellular matrix in the tumor, being the more compliant cell even though it resides in a stiffer matrix. Overall, the simultaneous mechanical characterization of the tissues constituents (cells and ECM) provided new support for diagnosis and offered alternative points of analysis for cancer mechanobiology. When the integrity of the mechanical cross-talk between cells and the extra-cellular matrix is disturbed cancer, along with other diseases, may initiate and progress. Here, we show how a new technique gives the opportunity to evaluate the mechanics of cells and the ECM at the same time. It was applied on surgically removed tissues of 10 patients affected by adenocarcinoma of the lung and a correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. Heterogeneity, Cell Biology and Tissue Mechanics of Pseudostratified Epithelia: Coordination of Cell Divisions and Growth in Tightly Packed Tissues.

    Science.gov (United States)

    Strzyz, P J; Matejcic, M; Norden, C

    2016-01-01

    Pseudostratified epithelia (PSE) are tightly packed proliferative tissues that are important precursors of the development of diverse organs in a plethora of species, invertebrate and vertebrate. PSE consist of elongated epithelial cells that are attached to the apical and basal side of the tissue. The nuclei of these cells undergo interkinetic nuclear migration (IKNM) which leads to all mitotic events taking place at the apical surface of the epithelium. In this review, we discuss the intricacies of proliferation in PSE, considering cell biological, as well as the physical aspects. First, we summarize the principles governing the invariability of apical nuclear migration and apical cell division as well as the importance of apical mitoses for tissue proliferation. Then, we focus on the mechanical and structural features of these tissues. Here, we discuss how the overall architecture of pseudostratified tissues changes with increased cell packing. Lastly, we consider possible mechanical cues resulting from these changes and their potential influence on cell proliferation. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. An impedance method for spatial sensing of 3D cell constructs – towards applications in tissue engineering

    DEFF Research Database (Denmark)

    Canali, Chiara; Mazzoni, Chiara; Larsen, Layla Bashir

    2015-01-01

    ) cells were encapsulated in gelatin to form artificial 3D cell constructs and detected when placed in different positions inside large gelatin scaffolds. Taken together, these results open new perspectives for impedance-based sensing technologies for non-invasive monitoring in tissue engineering...

  6. Optical clearing: impact of optical and dielectric properties of clearing solutions on pulmonary tissue mechanics.

    Science.gov (United States)

    Schwenninger, David; Priebe, Hans-Joachim; Schneider, Matthias; Runck, Hanna; Guttmann, Josef

    2017-07-01

    Optical clearing allows tissue visualization under preservation of organ integrity. Optical clearing of organs with a physiological change in three-dimensional geometry (such as the lung) would additionally allow visualization of macroscopic and microscopic tissue geometry. A prerequisite, however, is the preservation of the native tissue mechanics of the optically cleared lung tissue. We investigated the impact of optical and dielectric properties of clearing solutions on biomechanics and clearing potency in porcine tissue strips of healthy lungs. After fixation, bleaching, and rehydration, four methods of optical clearing were investigated using eight different protocols. The mechanical and optical properties of the cleared lung tissue strips were investigated by uniaxial tensile testing and by analyzing optical transparency and translucency for red, green, and blue light before, during, and after the biochemical optical clearing process. Fresh tissue strips were used as controls. Best balance between efficient clearing and preserved mechanics was found for clearing with a 1:1 mixture of dimethyl sulfoxide (DMSO) and aniline. Our findings show that 1 ) the degree of tissue transparency and translucency correlated with the refractive index of the clearing solution index ( r = 0.976, P = 0.0004; and r = 0.91, P = 0.0046, respectively), 2 ) tissue mechanics were affected by dehydration and the type of clearing solution, and 3 ) tissue biomechanics and geometry correlated with the dielectric constant of the clearing solution ( r = -0.98, P mechanics, our results help to compose optimal clearing solutions. In addition, the results allow conclusions on the molecular interaction of solvents with collagen fibers in tissue, thereby consolidating existing theories about the functionality of collagen. Copyright © 2017 the American Physiological Society.

  7. [Analysis of the mechanisms of minor occupational injuries in the construction industry in Spain].

    Science.gov (United States)

    Benavides, F G; Giráldez, M T; Castejón, E; Catot, N; Zaplana, M; Delclós, J; Benach, J; Gimeno, D

    2003-01-01

    The construction industry produces the highest number of occupational injuries in Spain (25.6%). Of these, 98.5% were minor injuries with 5 million workdays lost in 2000. This occurred even after the recent introduction of numerous health and occupational safety regulations. The objective of the present study was to identify the specific mechanisms of minor occupational injuries in the construction sector. In 2000, there were 235,853 minor occupational injuries in the construction industry. From these, injuries in general construction and civil engineering were selected (n = 155,044). These injuries affected both the total number of workers in the sector as well as bricklayers and unskilled construction workers. Insurance and financial activities (n = 2,019) were selected as a reference economic sector. Minor occupational injuries due to nontraumatic processes (heart attack, etc.) were taken as a control group (n = 167), assuming that the risk of nontraumatic processes was independent of economic activities. Odds ratios (OR) were adjusted by age, sex, years of work experience, type of employment and company size through nonconditional logistic regression models. The mechanisms with the highest risk of minor occupational lesions in construction workers as a group compared with employees in the financial sector were projection of fragments (OR = 33.0; 95% CI, 15.3-70.8) and being struck by objects (OR = 18.2; CI 95%, 9.7-34.1). These were also the most specific mechanisms of injury in the subgroup of bricklayers and unskilled construction workers. Activities aimed at preventing minor occupational injuries in the construction sector should be orientated towards these mechanisms, especially projection of fragments despite the low frequency of this mechanism compared with that of other mechanisms. Case-control design is a useful alternative approach for research into occupational injuries.

  8. Bayesian state space models for dynamic genetic network construction across multiple tissues.

    Science.gov (United States)

    Liang, Yulan; Kelemen, Arpad

    2016-08-01

    Construction of gene-gene interaction networks and potential pathways is a challenging and important problem in genomic research for complex diseases while estimating the dynamic changes of the temporal correlations and non-stationarity are the keys in this process. In this paper, we develop dynamic state space models with hierarchical Bayesian settings to tackle this challenge for inferring the dynamic profiles and genetic networks associated with disease treatments. We treat both the stochastic transition matrix and the observation matrix time-variant and include temporal correlation structures in the covariance matrix estimations in the multivariate Bayesian state space models. The unevenly spaced short time courses with unseen time points are treated as hidden state variables. Hierarchical Bayesian approaches with various prior and hyper-prior models with Monte Carlo Markov Chain and Gibbs sampling algorithms are used to estimate the model parameters and the hidden state variables. We apply the proposed Hierarchical Bayesian state space models to multiple tissues (liver, skeletal muscle, and kidney) Affymetrix time course data sets following corticosteroid (CS) drug administration. Both simulation and real data analysis results show that the genomic changes over time and gene-gene interaction in response to CS treatment can be well captured by the proposed models. The proposed dynamic Hierarchical Bayesian state space modeling approaches could be expanded and applied to other large scale genomic data, such as next generation sequence (NGS) combined with real time and time varying electronic health record (EHR) for more comprehensive and robust systematic and network based analysis in order to transform big biomedical data into predictions and diagnostics for precision medicine and personalized healthcare with better decision making and patient outcomes.

  9. Mechanisms of Hepatocyte Growth Factor Activation in Cancer Tissues

    International Nuclear Information System (INIS)

    Kawaguchi, Makiko; Kataoka, Hiroaki

    2014-01-01

    Hepatocyte growth factor/scatter factor (HGF/SF) plays critical roles in cancer progression through its specific receptor, MET. HGF/SF is usually synthesized and secreted as an inactive proform (pro-HGF/SF) by stromal cells, such as fibroblasts. Several serine proteases are reported to convert pro-HGF/SF to mature HGF/SF and among these, HGF activator (HGFA) and matriptase are the most potent activators. Increased activities of both proteases have been observed in various cancers. HGFA is synthesized mainly by the liver and secreted as an inactive pro-form. In cancer tissues, pro-HGFA is likely activated by thrombin and/or human kallikrein 1-related peptidase (KLK)-4 and KLK-5. Matriptase is a type II transmembrane serine protease that is expressed by most epithelial cells and is also synthesized as an inactive zymogen. Matriptase activation is likely to be mediated by autoactivation or by other trypsin-like proteases. Recent studies revealed that matriptase autoactivation is promoted by an acidic environment. Given the mildly acidic extracellular environment of solid tumors, matriptase activation may, thus, be accelerated in the tumor microenvironment. HGFA and matriptase activities are regulated by HGFA inhibitor (HAI)-1 (HAI-1) and/or HAI-2 in the pericellular microenvironment. HAIs may have an important role in cancer cell biology by regulating HGF/SF-activating proteases

  10. Mechanisms of Hepatocyte Growth Factor Activation in Cancer Tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kawaguchi, Makiko; Kataoka, Hiroaki, E-mail: mejina@med.miyazaki-u.ac.jp [Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

    2014-09-29

    Hepatocyte growth factor/scatter factor (HGF/SF) plays critical roles in cancer progression through its specific receptor, MET. HGF/SF is usually synthesized and secreted as an inactive proform (pro-HGF/SF) by stromal cells, such as fibroblasts. Several serine proteases are reported to convert pro-HGF/SF to mature HGF/SF and among these, HGF activator (HGFA) and matriptase are the most potent activators. Increased activities of both proteases have been observed in various cancers. HGFA is synthesized mainly by the liver and secreted as an inactive pro-form. In cancer tissues, pro-HGFA is likely activated by thrombin and/or human kallikrein 1-related peptidase (KLK)-4 and KLK-5. Matriptase is a type II transmembrane serine protease that is expressed by most epithelial cells and is also synthesized as an inactive zymogen. Matriptase activation is likely to be mediated by autoactivation or by other trypsin-like proteases. Recent studies revealed that matriptase autoactivation is promoted by an acidic environment. Given the mildly acidic extracellular environment of solid tumors, matriptase activation may, thus, be accelerated in the tumor microenvironment. HGFA and matriptase activities are regulated by HGFA inhibitor (HAI)-1 (HAI-1) and/or HAI-2 in the pericellular microenvironment. HAIs may have an important role in cancer cell biology by regulating HGF/SF-activating proteases.

  11. Mechanically Reinforced Catechol-Containing Hydrogels with Improved Tissue Gluing Performance

    Directory of Open Access Journals (Sweden)

    Jun Feng

    2017-11-01

    Full Text Available In situ forming hydrogels with catechol groups as tissue reactive functionalities are interesting bioinspired materials for tissue adhesion. Poly(ethylene glycol (PEG–catechol tissue glues have been intensively investigated for this purpose. Different cross-linking mechanisms (oxidative or metal complexation and cross-linking conditions (pH, oxidant concentration, etc. have been studied in order to optimize the curing kinetics and final cross-linking degree of the system. However, reported systems still show limited mechanical stability, as expected from a PEG network, and this fact limits their potential application to load bearing tissues. Here, we describe mechanically reinforced PEG–catechol adhesives showing excellent and tunable cohesive properties and adhesive performance to tissue in the presence of blood. We used collagen/PEG mixtures, eventually filled with hydroxyapatite nanoparticles. The composite hydrogels show far better mechanical performance than the individual components. It is noteworthy that the adhesion strength measured on skin covered with blood was >40 kPa, largely surpassing (>6 fold the performance of cyanoacrylate, fibrin, and PEG–catechol systems. Moreover, the mechanical and interfacial properties could be easily tuned by slight changes in the composition of the glue to adapt them to the particular properties of the tissue. The reported adhesive compositions can tune and improve cohesive and adhesive properties of PEG–catechol-based tissue glues for load-bearing surgery applications.

  12. Characterization of the mechanical properties of resected porcine organ tissue using optical fiber photoelastic polarimetry.

    Science.gov (United States)

    Hudnut, Alexa W; Babaei, Behzad; Liu, Sonya; Larson, Brent K; Mumenthaler, Shannon M; Armani, Andrea M

    2017-10-01

    Characterizing the mechanical behavior of living tissue presents an interesting challenge because the elasticity varies by eight orders of magnitude, from 50Pa to 5GPa. In the present work, a non-destructive optical fiber photoelastic polarimetry system is used to analyze the mechanical properties of resected samples from porcine liver, kidney, and pancreas. Using a quasi-linear viscoelastic fit, the elastic modulus values of the different organ systems are determined. They are in agreement with previous work. In addition, a histological assessment of compressed and uncompressed tissues confirms that the tissue is not damaged during testing.

  13. Mapping of Mechanical Strains and Stresses around Quiescent Engineered Three-Dimensional Epithelial Tissues

    Science.gov (United States)

    Gjorevski, Nikolce; Nelson, Celeste M.

    2012-01-01

    Understanding how physical signals guide biological processes requires qualitative and quantitative knowledge of the mechanical forces generated and sensed by cells in a physiologically realistic three-dimensional (3D) context. Here, we used computational modeling and engineered epithelial tissues of precise geometry to define the experimental parameters that are required to measure directly the mechanical stress profile of 3D tissues embedded within native type I collagen. We found that to calculate the stresses accurately in these settings, we had to account for mechanical heterogeneities within the matrix, which we visualized and quantified using confocal reflectance and atomic force microscopy. Using this technique, we were able to obtain traction forces at the epithelium-matrix interface, and to resolve and quantify patterns of mechanical stress throughout the surrounding matrix. We discovered that whereas single cells generate tension by contracting and pulling on the matrix, the contraction of multicellular tissues can also push against the matrix, causing emergent compression. Furthermore, tissue geometry defines the spatial distribution of mechanical stress across the epithelium, which communicates mechanically over distances spanning hundreds of micrometers. Spatially resolved mechanical maps can provide insight into the types and magnitudes of physical parameters that are sensed and interpreted by multicellular tissues during normal and pathological processes. PMID:22828342

  14. Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation

    Science.gov (United States)

    Niessen, Carien M.; Leckband, Deborah; Yap, Alpha S.

    2013-01-01

    This review addresses the cellular and molecular mechanisms of cadherin-based tissue morphogenesis. Tissue physiology is profoundly influenced by the distinctive organizations of cells in organs and tissues. In metazoa, adhesion receptors of the classical cadherin family play important roles in establishing and maintaining such tissue organization. Indeed, it is apparent that cadherins participate in a range of morphogenetic events that range from support of tissue integrity to dynamic cellular rearrangements. A comprehensive understanding of cadherin-based morphogenesis must then define the molecular and cellular mechanisms that support these distinct cadherin biologies. Here we focus on four key mechanistic elements: the molecular basis for adhesion through cadherin ectodomains; the regulation of cadherin expression at the cell surface; cooperation between cadherins and the actin cytoskeleton; and regulation by cell signaling. We discuss current progress and outline issues for further research in these fields. PMID:21527735

  15. Improved repair of bone defects with prevascularized tissue-engineered bones constructed in a perfusion bioreactor.

    Science.gov (United States)

    Li, De-Qiang; Li, Ming; Liu, Pei-Lai; Zhang, Yuan-Kai; Lu, Jian-Xi; Li, Jian-Min

    2014-10-01

    Vascularization of tissue-engineered bones is critical to achieving satisfactory repair of bone defects. The authors investigated the use of prevascularized tissue-engineered bone for repairing bone defects. The new bone was greater in the prevascularized group than in the non-vascularized group, indicating that prevascularized tissue-engineered bone improves the repair of bone defects. [Orthopedics. 2014; 37(10):685-690.]. Copyright 2014, SLACK Incorporated.

  16. A 'waterfall' transfer-based workflow for improved quality of tissue microarray construction and processing in breast cancer research.

    Science.gov (United States)

    Oberländer, M; Alkemade, H; Bünger, S; Ernst, F; Thorns, C; Braunschweig, T; Habermann, J K

    2014-07-01

    A major focus in cancer research is the identification of biomarkers for early diagnosis, therapy prediction and prognosis. Hereby, validation of target proteins on clinical samples is of high importance. Tissue microarrays (TMAs) represent an essential advancement for high-throughput analysis by assembling large numbers of tissue cores with high efficacy and comparability. However, limitations along TMA construction and processing exist. In our presented study, we had to overcome several obstacles in the construction and processing of high-density breast cancer TMAs to ensure good quality sections for further research. Exemplarily, 406 breast tissue cores from formalin-fixed and paraffin embedded samples of 245 patients were placed onto three recipient paraffin blocks. Sectioning was performed using a rotary microtome with a "waterfall" automated transfer system. Sections were stained by immunohistochemistry and immunofluorescence for nine proteins. The number and quality of cores after sectioning and staining was counted manually for each marker. In total, 97.1 % of all cores were available after sectioning, while further 96 % of the remaining cores were evaluable after staining. Thereby, normal tissue cores were more often lost compared to tumor tissue cores. Our workflow provides a robust method for manufacturing high-density breast cancer TMAs for subsequent IHC or IF staining without significant sample loss.

  17. Thermo-electrical equivalents for simulating the electro-mechanical behavior of biological tissue.

    Science.gov (United States)

    Cinelli, I; Duffy, M; McHugh, P E

    2015-01-01

    Equivalence is one of most popular techniques to simulate the behavior of systems governed by the same type of differential equation. In this case, a thermo-electrical equivalence is considered as a method for modelling the inter-dependence of electrical and mechanical phenomena in biological tissue. We seek to assess this approach for multi-scale models (from micro-structure to tissue scale) of biological media, such as nerve cells and cardiac tissue, in which the electrical charge distribution is modelled as a heat distribution in an equivalent thermal system. This procedure allows for the reduction in problem complexity and it facilitates the coupling of electrical and mechanical phenomena in an efficient and practical way. Although the findings of this analysis are mainly addressed towards the electro-mechanics of tissue within the biomedical domain, the same approach could be used in other studies in which a coupled finite element analysis is required.

  18. A method for quantifying mechanical properties of tissue following viral infection.

    Directory of Open Access Journals (Sweden)

    Vy Lam

    Full Text Available Viral infection and replication involves the reorganization of the actin network within the host cell. Actin plays a central role in the mechanical properties of cells. We have demonstrated a method to quantify changes in mechanical properties of fabricated model three-dimensional (3D connective tissue following viral infection. Using this method, we have characterized the impact of infection by the human herpesvirus, cytomegalovirus (HCMV. HCMV is a member of the herpesvirus family and infects a variety of cell types including fibroblasts. In the body, fibroblasts are necessary for maintaining connective tissue and function by creating mechanical force. Using this 3D connective tissue model, we observed that infection disrupted the cell's ability to generate force and reduced the cumulative contractile force of the tissue. The addition of HCMV viral particles in the absence of both viral gene expression and DNA replication was sufficient to disrupt tissue function. We observed that alterations of the mechanical properties are, in part, due to a disruption of the underlying complex actin microfilament network established by the embedded fibroblasts. Finally, we were able to prevent HCMV-mediated disruption of tissue function by the addition of human immune globulin against HCMV. This study demonstrates a method to quantify the impact of viral infection on mechanical properties which are not evident using conventional cell culture systems.

  19. Scaffoldless tissue-engineered dental pulp cell constructs for endodontic therapy.

    Science.gov (United States)

    Syed-Picard, F N; Ray, H L; Kumta, P N; Sfeir, C

    2014-03-01

    A major cause of apical periodontitis after endodontic treatment is the bacterial infiltration which could have been challenged by the presence of a vital pulp. In this study, self-assembled, scaffoldless, three-dimensional (3D) tissues were engineered from dental pulp cells (DPCs) and assessed as a device for pulp regeneration. These engineered tissues were placed into the canal space of human tooth root segments that were capped on one end with calcium phosphate cement, and the entire system was implanted subcutaneously into mice. Histological staining indicated that after three- and five-month implantations, tooth roots containing 3D scaffoldless engineered tissues maintained a cellular, fibrous tissue throughout, whereas empty tooth roots remained predominantly empty. Immunostaining indicated that the tissue found in the root canals containing scaffoldless DPC engineered tissues was vascular, as characterized by the expression of CD31, and contained odontoblast-like cells organized along the length of the root wall as assessed by immunostaining for dentin sialoprotein. This study shows that 3D self-assembled scaffoldless DPC engineered tissues can regenerate a vital dental pulp-like tissue in a tooth root canal system and are therefore promising for endodontic therapy.

  20. A nano-sandwich construct built with graphene nanosheets and carbon nanotubes enhances mechanical properties of hydroxyapatite–polyetheretherketone scaffolds

    Directory of Open Access Journals (Sweden)

    Feng P

    2016-07-01

    Full Text Available Pei Feng,1,* Shuping Peng,2,3,* Ping Wu,4 Chengde Gao,1 Wei Huang,1 Youwen Deng,5 Tao Xiao,5 Cijun Shuai1 1State Key Laboratory of High Performance Complex Manufacturing, 2The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, 3The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Cancer Research Institute, Xiangya Hospital, Central South University, Changsha, 4College of Chemistry, Xiangtan University, Xiangtan, 5Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China *These authors contributed equally to this work Abstract: A nano-sandwich construct was built by combining two-dimensional graphene nanosheets (GNSs and one-dimensional carbon nanotubes (CNTs to improve the mechanical properties of hydroxyapatite–polyetheretherketone (HAP–PEEK scaffolds for bone tissue engineering. In this nano-sandwich construct, the long tubular CNTs penetrated the interlayers of graphene and prevented their aggregation, increasing the effective contact area between the construct and matrix. The combination of GNSs and CNTs in a weight ratio of 2:8 facilitated the dispersion of each other and provided a synergetic effect in enhancing the mechanical properties. The compressive strength and modulus of the scaffolds were increased by 63.58% and 56.54% at this time compared with those of HAP–PEEK scaffolds, respectively. The carbon-based fillers, pulling out and bridging, were also clearly observed in the matrix. Moreover, the dangling of CNTs and their entangling with GNSs further reinforced the mechanical properties. Furthermore, apatite layer formed on the scaffold surface after immersing in simulated body fluid, and the cells attached and spread well on the surface of the scaffolds and displayed good viability, proliferation, and differentiation. These evidence indicate that the HAP–PEEK scaffolds enhanced by GNSs and CNTs are a

  1. Mechanisms of the Stimulation of Import Substitution in the Construction Industry

    Directory of Open Access Journals (Sweden)

    Svetlana Nikolayevna Kotlyarova

    2016-12-01

    Full Text Available The issues of the dependence on imports and import substitution are the major factors in the development of the domestic economy. The subject matter of the research is the dependence of construction industry on imports in the area of foreign technology, it is aimed at identifying the scope of the problem and justifying the mechanisms to overcome it. The article substantiates the relevance and importance of import substitution in the production of construction materials and equipment. Import substitution in the construction industry can be implemented in two main ways, requiring different approaches in supporting and encouraging. Firstly, there is the substitution of products used in construction, aimed at minimizing the risk of disruption of the supply of imported products for construction purposes and the predominant use of domestic analogues of imported products for construction purposes. Secondly, there is the substitution in the technologies of production of goods used in construction, focused on stimulating the development of the domestic production of competitive products and technological and managerial modernization of the construction materials industry, construction industry. The process of import substitution in the construction industry have a number of limitations. In this connection, the article discusses the opportunities and constraints for import substitution. A special attention is paid to the practice of the formation of regional construction clusters as a tool of implementing the policy of import substitution. The purposes and principles of the development of clusters, sources of initiatives, used systems of transfer and knowledge and innovations are considered critically. The conclusion is made about the need for the strategic development of new products for the construction market and domestic research and development projects within the framework of cross-sectoral clusters. The basic forms of state support required for the

  2. Pivotal role of tissue plasminogen activator in the mechanism of action of electroconvulsive therapy.

    Science.gov (United States)

    Hoirisch-Clapauch, Silvia; Mezzasalma, Marco A U; Nardi, Antonio E

    2014-02-01

    Electroconvulsive therapy is an important treatment option for major depressive disorders, acute mania, mood disorders with psychotic features, and catatonia. Several hypotheses have been proposed as electroconvulsive therapy's mechanism of action. Our hypothesis involves many converging pathways facilitated by increased synthesis and release of tissue-plasminogen activator. Human and animal experiments have shown that tissue-plasminogen activator participates in many mechanisms of action of electroconvulsive therapy or its animal variant, electroconvulsive stimulus, including improved N-methyl-D-aspartate receptor-mediated signaling, activation of both brain-derived neurotrophic factor and vascular endothelial growth factor, increased bioavailability of zinc, purinergic release, and increased mobility of dendritic spines. As a result, tissue-plasminogen activator helps promote neurogenesis in limbic structures, modulates synaptic transmission and plasticity, improves cognitive function, and mediates antidepressant effects. Notably, electroconvulsive therapy seems to influence tissue-plasminogen activator metabolism. For example, electroconvulsive stimulus increases the expression of glutamate decarboxylase 65 isoform in γ-aminobutyric acid-releasing neurons, which enhances the release of tissue-plasminogen activator, and the expression of p11, a protein involved in plasminogen and tissue-plasminogen activator assembling. This paper reviews how electroconvulsive therapy correlates with tissue-plasminogen activator. We suggest that interventions aiming at increasing tissue-plasminogen activator levels or its bioavailability - such as daily aerobic exercises together with a carbohydrate-restricted diet, or normalization of homocysteine levels - be evaluated in controlled studies assessing response and remission duration in patients who undergo electroconvulsive therapy.

  3. Inference of Cell Mechanics in Heterogeneous Epithelial Tissue Based on Multivariate Clone Shape Quantification

    Science.gov (United States)

    Tsuboi, Alice; Umetsu, Daiki; Kuranaga, Erina; Fujimoto, Koichi

    2017-01-01

    Cell populations in multicellular organisms show genetic and non-genetic heterogeneity, even in undifferentiated tissues of multipotent cells during development and tumorigenesis. The heterogeneity causes difference of mechanical properties, such as, cell bond tension or adhesion, at the cell–cell interface, which determine the shape of clonal population boundaries via cell sorting or mixing. The boundary shape could alter the degree of cell–cell contacts and thus influence the physiological consequences of sorting or mixing at the boundary (e.g., tumor suppression or progression), suggesting that the cell mechanics could help clarify the physiology of heterogeneous tissues. While precise inference of mechanical tension loaded at each cell–cell contacts has been extensively developed, there has been little progress on how to distinguish the population-boundary geometry and identify the cause of geometry in heterogeneous tissues. We developed a pipeline by combining multivariate analysis of clone shape with tissue mechanical simulations. We examined clones with four different genotypes within Drosophila wing imaginal discs: wild-type, tartan (trn) overexpression, hibris (hbs) overexpression, and Eph RNAi. Although the clones were previously known to exhibit smoothed or convoluted morphologies, their mechanical properties were unknown. By applying a multivariate analysis to multiple criteria used to quantify the clone shapes based on individual cell shapes, we found the optimal criteria to distinguish not only among the four genotypes, but also non-genetic heterogeneity from genetic one. The efficient segregation of clone shape enabled us to quantitatively compare experimental data with tissue mechanical simulations. As a result, we identified the mechanical basis contributed to clone shape of distinct genotypes. The present pipeline will promote the understanding of the functions of mechanical interactions in heterogeneous tissue in a non-invasive manner. PMID

  4. A Tissue-Engineered Muscle Repair Construct for Functional Restoration of an Irrecoverable Muscle Injury in a Murine Model

    Science.gov (United States)

    2011-07-28

    level of morbidity, permanent functional disfigurement, and the as- sociated loss of quality of life and self - esteem . In this sce- nario, the ability... cosmetic and functional deficits. In this regard, current management of VML injuries in- volves the use of existing host tissue to construct muscular flaps... surgery and outcome. Plast Reconstr Surg 102, 711, 1998. 18. Lin, C.H., Wei, F.C., Levin, L.S., and Chen, M.C. Donor site morbidity comparison between

  5. [THE INFLUENCE OF MODERN ORTHOPEDIC CONSTRUCTIONS ON THE CONDITION OF PERIODONTAL TISSUES OF PATIENTS WITH GENERALIZED PERIODONTITIS].

    Science.gov (United States)

    Kochkina, N A

    2015-01-01

    Patients with generalized periodontitis studied the effect of the partial removable denture made from acrylic met and thermoplastic materials on the state of periodontal tissues. The results of clin- ical studies have shown a significant improvement in oral hygiene, positive change in activity indi- cators current generalized periodontitis: patients for whom orthopedic constructions are made of thermoplastic mass, reduce the depth of periodontl pockets, tooth mobility, bleeding and inflamma- tion of the interdental, papillae and the gingival margin.

  6. Mechanical modulation of nascent stem cell lineage commitment in tissue engineering scaffolds.

    Science.gov (United States)

    Song, Min Jae; Dean, David; Knothe Tate, Melissa L

    2013-07-01

    Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially resolved mechanical cues to stem cells seeded within. When subjected to a constant magnitude global flow regime, the local scaffold geometry dictates the magnitudes of mechanical stresses and strains experienced by a given cell, and in a spatially resolved fashion, similar to patterning during morphogenesis. In addition, early markers of mesenchymal stem cell lineage commitment relate significantly to the local mechanical environment of the cell. Finally, by plotting the range of stress-strain states for all data corresponding to nascent cell lineage commitment (95% CI), we begin to "map the mechanome", defining stress-strain states most conducive to targeted cell fates. In sum, we provide a library of reference mechanical cues that can be delivered to cells seeded on tissue engineering scaffolds to guide target tissue phenotypes in a temporally and spatially resolved manner. Knowledge of these effects allows for prospective scaffold design optimization using virtual models prior to prototyping and clinical implementation. Finally, this approach enables the development of next generation scaffolds cum delivery devices for genesis of complex tissues with heterogenous properties, e.g., organs, joints or interface tissues such as growth plates. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Construction

    Science.gov (United States)

    2002-01-01

    Harbor Deepening Project, Jacksonville, FL Palm Valley Bridge Project, Jacksonville, FL Rotary Club of San Juan, San Juan, PR Tren Urbano Subway...David. What is nanotechnology? What are its implications for construction?, Foresight/CRISP Workshop on Nanotechnology, Royal Society of Arts

  8. Construction and characteristics of questionnaire for the assessment of defense mechanisms: MOD

    Directory of Open Access Journals (Sweden)

    Džamonja-Ignjatović Tamara

    2014-01-01

    Full Text Available Defense mechanisms are psychological constructs of key importance for the assessment of personality and planning therapeutic process. Their assessment is mainly based on interview, observation and projective techniques. Questionnaires, as the self-assessment techniques, apparently are not suitable method for unconscious processes such as defense mechanisms. The paper presents the results of construction of the questionnaire for the assessment of defense mechanisms, abbreviated called MOD (Mechanisms of Defense, which represents an attempt to clarify conceptualization and operationalization of these constructs through a variety of behavioral and emotional manifestations, personal attitudes and beliefs, patterns of interpersonal relationships and feedback from environment. Research objectives included testing of metric characteristics and the factor structure of the questionnaire, as well as its validity for differentiating subjects from clinical and non-clinical populations. The questionnaire has 110 items assessed at the 5-point Likert scale for evaluation of 20 defense mechanisms. The sample consisted of 194 subjects of both sexes, of which 136 students of psychology and social work and 58 nonpsychotic patients from clinical populations. The results showed that the reliability of the scale varies from high to unsatisfactory (Cronbach alpha .82- .35, although for most subscales is around .65-.70. The most of defense mechanisms has one factor structure, whereas from about a third of the subscales two principal components were isolated. Analysis of the structure of mature defense mechanisms clearly derived out four factors corresponding to the presumed mechanisms of defense, while for the groups of neurotic and immature mechanisms were not obtained pure solutions. The questionnaire successfully differentiate clinical from non-clinical sample, based on higher scores on mature and lower scores on immature mechanisms, while the groups did not differ

  9. Dynamic culture of a thermosensitive collagen hydrogel as an extracellular matrix improves the construction of tissue-engineered peripheral nerve.

    Science.gov (United States)

    Huang, Lanfeng; Li, Rui; Liu, Wanguo; Dai, Jin; Du, Zhenwu; Wang, Xiaonan; Ma, Jianchao; Zhao, Jinsong

    2014-07-15

    Tissue engineering technologies offer new treatment strategies for the repair of peripheral nerve injury, but cell loss between seeding and adhesion to the scaffold remains inevitable. A thermosensitive collagen hydrogel was used as an extracellular matrix in this study and combined with bone marrow mesenchymal stem cells to construct tissue-engineered peripheral nerve composites in vitro. Dynamic culture was performed at an oscillating frequency of 0.5 Hz and 35° swing angle above and below the horizontal plane. The results demonstrated that bone marrow mesenchymal stem cells formed membrane-like structures around the poly-L-lactic acid scaffolds and exhibited regular alignment on the composite surface. Collagen was used to fill in the pores, and seeded cells adhered onto the poly-L-lactic acid fibers. The DNA content of the bone marrow mesenchymal stem cells was higher in the composites constructed with a thermosensitive collagen hydrogel compared with that in collagen I scaffold controls. The cellular DNA content was also higher in the thermosensitive collagen hydrogel composites constructed with the thermosensitive collagen hydrogel in dynamic culture than that in static culture. These results indicate that tissue-engineered composites formed with thermosensitive collagen hydrogel in dynamic culture can maintain larger numbers of seeded cells by avoiding cell loss during the initial adhesion stage. Moreover, seeded cells were distributed throughout the material.

  10. SEARCHING FOR ELECTRICAL PROPERTIES, PHENOMENA AND MECHANISMS IN THE CONSTRUCTION AND FUNCTION OF CHROMOSOMES

    Directory of Open Access Journals (Sweden)

    Ivan Kanev

    2013-03-01

    Full Text Available Our studies reveal previously unidentified electrical properties of chromosomes: (1 chromosomes are amazingly similar in construction and function to electrical transformers; (2 chromosomes possess in their construction and function, components similar to those of electric generators, conductors, condensers, switches, and other components of electrical circuits; (3 chromosomes demonstrate in nano-scale level electromagnetic interactions, resonance, fusion and other phenomena similar to those described by equations in classical physics. These electrical properties and phenomena provide a possible explanation for unclear and poorly understood mechanisms in clinical genetics including: (a electrically based mechanisms responsible for breaks, translocations, fusions, and other chromosomal abnormalities associated with cancer, intellectual disability, infertility, pregnancy loss, Down syndrome, and other genetic disorders; (b electrically based mechanisms involved in crossing over, non-disjunction and other events during meiosis and mitosis; (c mechanisms demonstrating heterochromatin to be electrically active and genetically important.

  11. Effects of mechanical loading on human mesenchymal stem cells for cartilage tissue engineering.

    Science.gov (United States)

    Choi, Jane Ru; Yong, Kar Wey; Choi, Jean Yu

    2018-03-01

    Today, articular cartilage damage is a major health problem, affecting people of all ages. The existing conventional articular cartilage repair techniques, such as autologous chondrocyte implantation (ACI), microfracture, and mosaicplasty, have many shortcomings which negatively affect their clinical outcomes. Therefore, it is essential to develop an alternative and efficient articular repair technique that can address those shortcomings. Cartilage tissue engineering, which aims to create a tissue-engineered cartilage derived from human mesenchymal stem cells (MSCs), shows great promise for improving articular cartilage defect therapy. However, the use of tissue-engineered cartilage for the clinical therapy of articular cartilage defect still remains challenging. Despite the importance of mechanical loading to create a functional cartilage has been well demonstrated, the specific type of mechanical loading and its optimal loading regime is still under investigation. This review summarizes the most recent advances in the effects of mechanical loading on human MSCs. First, the existing conventional articular repair techniques and their shortcomings are highlighted. The important parameters for the evaluation of the tissue-engineered cartilage, including chondrogenic and hypertrophic differentiation of human MSCs are briefly discussed. The influence of mechanical loading on human MSCs is subsequently reviewed and the possible mechanotransduction signaling is highlighted. The development of non-hypertrophic chondrogenesis in response to the changing mechanical microenvironment will aid in the establishment of a tissue-engineered cartilage for efficient articular cartilage repair. © 2017 Wiley Periodicals, Inc.

  12. Raman spectroscopic analysis of human tissue engineered oral mucosa constructs (EVPOME) perturbed by physical and biochemical methods

    Science.gov (United States)

    Khmaladze, Alexander; Ganguly, Arindam; Raghavan, Mekhala; Kuo, Shiuhyang; Cole, Jacqueline H.; Marcelo, Cynthia L.; Feinberg, Stephen E.; Izumi, Kenji; Morris, Michael D.

    2012-01-01

    We show the application of near-infrared Raman Spectroscopy to in-vitro monitoring of the viability of tissue constructs (EVPOMEs). During their two week production period EVPOME may encounter thermal, chemical or biochemical stresses that could cause development to cease, rendering the affected constructs useless. We discuss the development of a Raman spectroscopic technique to study EVPOMEs noninvasively, with the ultimate goal of applying it in-vivo. We identify Raman spectroscopic failure indicators for EVPOMEs, which are stressed by temperature, and discuss the implications of varying calcium concentration and pre-treatment of the human keratinocytes with Rapamycin. In particular, Raman spectra show correlation of the peak height ratios of CH2 deformation to phenylalanine ring breathing, providing a Raman metric to distinguish between viable and nonviable constructs. We also show the results of singular value decomposition analysis, demonstrating the applicability of Raman spectroscopic technique to both distinguish between stressed and non-stressed EVPOME constructs, as well as between EVPOMEs and bare AlloDerm® substrates, on which the oral keratinocytes have been cultured. We also discuss complications arising from non-uniform thickness of the AlloDerm® substrate and the cultured constructs, as well as sampling protocols used to detect local stress and other problems that may be encountered in the constructs.

  13. Interleukin-6 blockade attenuates lung cancer tissue construction integrated by cancer stem cells

    OpenAIRE

    Ogawa, Hiroyuki; Koyanagi-Aoi, Michiyo; Otani, Kyoko; Zen, Yoh; Maniwa, Yoshimasa; Aoi, Takashi

    2017-01-01

    In the present study, we successfully generated lung cancer stem cell (CSC)-like cells by introducing a small set of transcription factors into a lung cancer cell line. In addition to properties that are conventionally referred to as CSC properties, the lung induced CSCs exhibited the ability to form lung cancer-like tissues in vitro with vascular cells and mesenchymal stem cells, which showed structures and immunohistological patterns that were similar to human lung cancer tissues. We named ...

  14. The development of the collagen fibre network in tissue-engineered cartilage constructs in vivo. Engineered cartilage reorganises fibre network

    Directory of Open Access Journals (Sweden)

    H Paetzold

    2012-04-01

    Full Text Available For long term durability of tissue-engineered cartilage implanted in vivo, the development of the collagen fibre network orientation is essential as well as the distribution of collagen, since expanded chondrocytes are known to synthesise collagen type I. Typically, these properties differ strongly between native and tissue-engineered cartilage. Nonetheless, the clinical results of a pilot study with implanted tissue-engineered cartilage in pigs were surprisingly good. The purpose of this study was therefore to analyse if the structure and composition of the artificial cartilage tissue changes in the first 52 weeks after implantation. Thus, collagen network orientation and collagen type distribution in tissue-engineered cartilage-carrier-constructs implanted in the knee joints of Göttinger minipigs for 2, 26 or 52 weeks have been further investigated by processing digitised microscopy images of histological sections. The comparison to native cartilage demonstrated that fibre orientation over the cartilage depth has a clear tendency towards native cartilage with increasing time of implantation. After 2 weeks, the collagen fibres of the superficial zone were oriented parallel to the articular surface with little anisotropy present in the middle and deep zones. Overall, fibre orientation and collagen distribution within the implants were less homogenous than in native cartilage tissue. Despite a relatively low number of specimens, the consistent observation of a continuous approximation to native tissue is very promising and suggests that it may not be necessary to engineer the perfect tissue for implantation but rather to provide an intermediate solution to help the body to heal itself.

  15. The development of the collagen fibre network in tissue-engineered cartilage constructs in vivo. Engineered cartilage reorganises fibre network.

    Science.gov (United States)

    Paetzold, H; Goepfert, C; Huber, G; Hoenig, E; Pörtner, R; Schilling, A F; Meenen, N M; Morlock, M M

    2012-04-05

    For long term durability of tissue-engineered cartilage implanted in vivo, the development of the collagen fibre network orientation is essential as well as the distribution of collagen, since expanded chondrocytes are known to synthesise collagen type I. Typically, these properties differ strongly between native and tissue-engineered cartilage. Nonetheless, the clinical results of a pilot study with implanted tissue-engineered cartilage in pigs were surprisingly good. The purpose of this study was therefore to analyse if the structure and composition of the artificial cartilage tissue changes in the first 52 weeks after implantation. Thus, collagen network orientation and collagen type distribution in tissue-engineered cartilage-carrier-constructs implanted in the knee joints of Göttinger minipigs for 2, 26 or 52 weeks have been further investigated by processing digitised microscopy images of histological sections. The comparison to native cartilage demonstrated that fibre orientation over the cartilage depth has a clear tendency towards native cartilage with increasing time of implantation. After 2 weeks, the collagen fibres of the superficial zone were oriented parallel to the articular surface with little anisotropy present in the middle and deep zones. Overall, fibre orientation and collagen distribution within the implants were less homogenous than in native cartilage tissue. Despite a relatively low number of specimens, the consistent observation of a continuous approximation to native tissue is very promising and suggests that it may not be necessary to engineer the perfect tissue for implantation but rather to provide an intermediate solution to help the body to heal itself.

  16. Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue.

    Science.gov (United States)

    Gautieri, Alfonso; Passini, Fabian S; Silván, Unai; Guizar-Sicairos, Manuel; Carimati, Giulia; Volpi, Piero; Moretti, Matteo; Schoenhuber, Herbert; Redaelli, Alberto; Berli, Martin; Snedeker, Jess G

    2017-05-01

    Concurrent with a progressive loss of regenerative capacity, connective tissue aging is characterized by a progressive accumulation of Advanced Glycation End-products (AGEs). Besides being part of the typical aging process, type II diabetics are particularly affected by AGE accumulation due to abnormally high levels of systemic glucose that increases the glycation rate of long-lived proteins such as collagen. Although AGEs are associated with a wide range of clinical disorders, the mechanisms by which AGEs contribute to connective tissue disease in aging and diabetes are still poorly understood. The present study harnesses advanced multiscale imaging techniques to characterize a widely employed in vitro model of ribose induced collagen aging and further benchmarks these data against experiments on native human tissues from donors of different age. These efforts yield unprecedented insight into the mechanical changes in collagen tissues across hierarchical scales from molecular, to fiber, to tissue-levels. We observed a linear increase in molecular spacing (from 1.45nm to 1.5nm) and a decrease in the D-period length (from 67.5nm to 67.1nm) in aged tissues, both using the ribose model of in vitro glycation and in native human probes. Multiscale mechanical analysis of in vitro glycated tendons strongly suggests that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and fibril-fibril sliding. This study lays an important foundation for interpreting the functional and biological effects of AGEs in collagen connective tissues, by exploiting experimental models of AGEs crosslinking and benchmarking them for the first time against endogenous AGEs in native tissue. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  17. The Construction of Causal Schemes: Learning Mechanisms at the Knowledge Level

    Science.gov (United States)

    diSessa, Andrea A.

    2014-01-01

    This work uses microgenetic study of classroom learning to illuminate (1) the role of pre-instructional student knowledge in the construction of normative scientific knowledge, and (2) the learning mechanisms that drive change. Three enactments of an instructional sequence designed to lead to a scientific understanding of thermal equilibration are…

  18. Removal of pharmaceutically active compounds in constructed wetlands: mechanisms and application

    NARCIS (Netherlands)

    He, Yujie

    2017-01-01

    A constructed wetland (CW) is an integrated and enhanced version of natural ecosystem for fate and transport of pharmaceutically active compounds (PhAC). This thesis demonstrates removal mechanisms of PhACs in CWs and their application as post-treatment processes to eliminate PhACs from

  19. Conception and construction rules for mechanical components of PWR nuclear island

    International Nuclear Information System (INIS)

    1988-06-01

    These rules of conception and construction for mechanical components of PWR nuclear island used in France are divided into 5 tomes bearing on: Tome 1: components of nuclear islands - Tome 2: materials - Tome 3: control methods - Tome 4: welding - Tome 5: fabrication [fr

  20. Capnographic Parameters in Ventilated Patients: Correspondence with Airway and Lung Tissue Mechanics.

    Science.gov (United States)

    Csorba, Zsofia; Petak, Ferenc; Nevery, Kitti; Tolnai, Jozsef; Balogh, Adam L; Rarosi, Ferenc; Fodor, Gergely H; Babik, Barna

    2016-05-01

    Although the mechanical status of the lungs affects the shape of the capnogram, the relations between the capnographic parameters and those reflecting the airway and lung tissue mechanics have not been established in mechanically ventilated patients. We, therefore, set out to characterize how the mechanical properties of the airways and lung tissues modify the indices obtained from the different phases of the time and volumetric capnograms and how the lung mechanical changes are reflected in the altered capnographic parameters after a cardiopulmonary bypass (CPB). Anesthetized, mechanically ventilated patients (n = 101) undergoing heart surgery were studied in a prospective consecutive cross-sectional study under the open-chest condition before and 5 minutes after CPB. Forced oscillation technique was applied to measure airway resistance (Raw), tissue damping (G), and elastance (H). Time and volumetric capnography were performed to assess parameters reflecting the phase II (SII) and phase III slopes (SIII), their transition (D2min), the dead-space indices according to Fowler, Bohr, and Enghoff and the intrapulmonary shunt. Before CPB, SII and D2min exhibited the closest (P = 0.006) associations with H (0.65 and -0.57; P elastic recoil, whereas the effect of airway patency on SIII dominates over the lung tissue stiffness. However, severe deterioration in lung resistance or elastance affects both capnogram slopes.

  1. Regional mechanical properties of human brain tissue for computational models of traumatic brain injury.

    Science.gov (United States)

    Finan, John D; Sundaresh, Sowmya N; Elkin, Benjamin S; McKhann, Guy M; Morrison, Barclay

    2017-06-01

    To determine viscoelastic shear moduli, stress relaxation indentation tests were performed on samples of human brain tissue resected in the course of epilepsy surgery. Through the use of a 500µm diameter indenter, regional mechanical properties were measured in cortical grey and white matter and subregions of the hippocampus. All regions were highly viscoelastic. Cortical grey matter was significantly more compliant than the white matter or hippocampus which were similar in modulus. Although shear modulus was not correlated with the age of the donor, cortex from male donors was significantly stiffer than from female donors. The presented material properties will help to populate finite element models of the brain as they become more anatomically detailed. We present the first mechanical characterization of fresh, post-operative human brain tissue using an indentation loading mode. Indentation generates highly localized data, allowing structure-specific mechanical properties to be determined from small tissue samples resected during surgery. It also avoids pitfalls of cadaveric tissue and allows data to be collected before degenerative processes alter mechanical properties. To correctly predict traumatic brain injury, finite element models must calculate intracranial deformation during head impact. The functional consequences of injury depend on the anatomical structures injured. Therefore, morbidity depends on the distribution of deformation across structures. Accurate prediction of structure-specific deformation requires structure-specific mechanical properties. This data will facilitate deeper understanding of the physical mechanisms that lead to traumatic brain injury. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  2. Can plantar soft tissue mechanics enhance prognosis of diabetic foot ulcer?

    Science.gov (United States)

    Naemi, R; Chatzistergos, P; Suresh, S; Sundar, L; Chockalingam, N; Ramachandran, A

    2017-04-01

    To investigate if the assessment of the mechanical properties of plantar soft tissue can increase the accuracy of predicting Diabetic Foot Ulceration (DFU). 40 patients with diabetic neuropathy and no DFU were recruited. Commonly assessed clinical parameters along with plantar soft tissue stiffness and thickness were measured at baseline using ultrasound elastography technique. 7 patients developed foot ulceration during a 12months follow-up. Logistic regression was used to identify parameters that contribute to predicting the DFU incidence. The effect of using parameters related to the mechanical behaviour of plantar soft tissue on the specificity, sensitivity, prediction strength and accuracy of the predicting models for DFU was assessed. Patients with higher plantar soft tissue thickness and lower stiffness at the 1st Metatarsal head area showed an increased risk of DFU. Adding plantar soft tissue stiffness and thickness to the model improved its specificity (by 3%), sensitivity (by 14%), prediction accuracy (by 5%) and prognosis strength (by 1%). The model containing all predictors was able to effectively (χ 2 (8, N=40)=17.55, P<0.05) distinguish between the patients with and without DFU incidence. The mechanical properties of plantar soft tissue can be used to improve the predictability of DFU in moderate/high risk patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Design considerations and challenges for mechanical stretch bioreactors in tissue engineering.

    Science.gov (United States)

    Lei, Ying; Ferdous, Zannatul

    2016-05-01

    With the increase in average life expectancy and growing aging population, lack of functional grafts for replacement surgeries has become a severe problem. Engineered tissues are a promising alternative to this problem because they can mimic the physiological function of the native tissues and be cultured on demand. Cyclic stretch is important for developing many engineered tissues such as hearts, heart valves, muscles, and bones. Thus a variety of stretch bioreactors and corresponding scaffolds have been designed and tested to study the underlying mechanism of tissue formation and to optimize the mechanical conditions applied to the engineered tissues. In this review, we look at various designs of stretch bioreactors and common scaffolds and offer insights for future improvements in tissue engineering applications. First, we summarize the requirements and common configuration of stretch bioreactors. Next, we present the features of different actuating and motion transforming systems and their applications. Since most bioreactors must measure detailed distributions of loads and deformations on engineered tissues, techniques with high accuracy, precision, and frequency have been developed. We also cover the key points in designing culture chambers, nutrition exchanging systems, and regimens used for specific tissues. Since scaffolds are essential for providing biophysical microenvironments for residing cells, we discuss materials and technologies used in fabricating scaffolds to mimic anisotropic native tissues, including decellularized tissues, hydrogels, biocompatible polymers, electrospinning, and 3D bioprinting techniques. Finally, we present the potential future directions for improving stretch bioreactors and scaffolds. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:543-553, 2016. © 2016 American Institute of Chemical Engineers.

  4. Changes in diffusion properties of biological tissues associated with mechanical strain

    International Nuclear Information System (INIS)

    Tanaka, Kenichiro; Imae, T.; Mima, Kazuo; Sekino, Masaki; Ohsaki, Hiroyuki; Ueno, Shogo

    2007-01-01

    Mechanical strain in biological tissues causes a change in the diffusion properties of water molecules. This paper proposes a method of estimating mechanical strain in biological tissues using diffusion magnetic resonance imaging (MRI). Measurements were carried out on uncompressed and compressed chicken skeletal muscles. A theoretical model of the diffusion of water molecules in muscle fibers was derived based on Tanner's equation. Diameter of the muscle fibers was estimated by fitting the model equation to the measured signals. Changes in the mean diffusivity (MD), the fractional anisotropy (FA), and diameter of the muscle fiber did not have any statistical significance. The intracellular diffusion coefficient (D int ) was changed by mechanical strain (p<.05). This method has potential applications in the quantitative evaluation of strain in biological tissues, a though it poses several technical challenges. (author)

  5. Contraction and elongation: Mechanics underlying cell boundary deformations in epithelial tissue.

    Science.gov (United States)

    Hara, Yusuke

    2017-06-01

    The cell-cell boundaries of epithelial cells form cellular frameworks at the apical side of tissues. Deformations in these boundaries, for example, boundary contraction and elongation, and the associated forces form the mechanical basis of epithelial tissue morphogenesis. In this review, using data from recent Drosophila studies on cell boundary contraction and elongation, I provide an overview of the mechanism underlying the bi-directional deformations in the epithelial cell boundary, that are sustained by biased accumulations of junctional and apico-medial non-muscle myosin II. Moreover, how the junctional tensions exist on cell boundaries in different boundary dynamics and morphologies are discussed. Finally, some future perspectives on how recent knowledge about single cell boundary-level mechanics will contribute to our understanding of epithelial tissue morphogenesis are discussed. © 2017 Japanese Society of Developmental Biologists.

  6. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

    International Nuclear Information System (INIS)

    Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L.

    2014-01-01

    To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

  7. Mechanical Activation of Adipose Tissue and Derived Mesenchymal Stem Cells: Novel Anti-Inflammatory Properties.

    Science.gov (United States)

    Carelli, Stephana; Colli, Mattia; Vinci, Valeriano; Caviggioli, Fabio; Klinger, Marco; Gorio, Alfredo

    2018-01-16

    The adipose tissue is a source of inflammatory proteins, such as TNF, IL-6, and CXCL8. Most of their production occurs in macrophages that act as scavengers of dying adipocytes. The application of an orbital mechanical force for 6-10 min at 97 g to the adipose tissue, lipoaspirated and treated according to Coleman procedures, abolishes the expression of TNF-α and stimulates the expression of the anti-inflammatory protein TNF-stimulated gene-6 (TSG-6). This protein had protective and anti-inflammatory effects when applied to animal models of rheumatic diseases. We examined biopsy, lipoaspirate, and mechanically activated fat and observed that in addition to the increased TSG-6, Sox2, Nanog, and Oct4 were also strongly augmented by mechanical activation, suggesting an effect on stromal cell stemness. Human adipose tissue-derived mesenchymal stem cells (hADSCs), produced from activated fat, grow and differentiate normally with proper cell surface markers and chromosomal integrity, but their anti-inflammatory action is far superior compared to those mesenchymal stem cells (MSCs) obtained from lipoaspirate. The expression and release of inflammatory cytokines from THP-1 cells was totally abolished in mechanically activated adipose tissue-derived hADSCs. In conclusion, we report that the orbital shaking of adipose tissue enhances its anti-inflammatory properties, and derived MSCs maintain such enhanced activity.

  8. Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography.

    Science.gov (United States)

    Guertler, Charlotte A; Okamoto, Ruth J; Schmidt, John L; Badachhape, Andrew A; Johnson, Curtis L; Bayly, Philip V

    2018-03-01

    The mechanical properties of brain tissue in vivo determine the response of the brain to rapid skull acceleration. These properties are thus of great interest to the developers of mathematical models of traumatic brain injury (TBI) or neurosurgical simulations. Animal models provide valuable insight that can improve TBI modeling. In this study we compare estimates of mechanical properties of the Yucatan mini-pig brain in vivo and ex vivo using magnetic resonance elastography (MRE) at multiple frequencies. MRE allows estimations of properties in soft tissue, either in vivo or ex vivo, by imaging harmonic shear wave propagation. Most direct measurements of brain mechanical properties have been performed using samples of brain tissue ex vivo. It has been observed that direct estimates of brain mechanical properties depend on the frequency and amplitude of loading, as well as the time post-mortem and condition of the sample. Using MRE in the same animals at overlapping frequencies, we observe that porcine brain tissue in vivo appears stiffer than porcine brain tissue samples ex vivo at frequencies of 100 Hz and 125 Hz, but measurements show closer agreement at lower frequencies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Skin equivalent tissue-engineered construct: co-cultured fibroblasts/ keratinocytes on 3D matrices of sericin hope cocoons.

    Science.gov (United States)

    Nayak, Sunita; Dey, Sancharika; Kundu, Subhas C

    2013-01-01

    The development of effective and alternative tissue-engineered skin replacements to autografts, allografts and xenografts has became a clinical requirement due to the problems related to source of donor tissue and the perceived risk of disease transmission. In the present study 3D tissue engineered construct of sericin is developed using co-culture of keratinocytes on the upper surface of the fabricated matrices and with fibroblasts on lower surface. Sericin is obtained from "Sericin Hope" silkworm of Bombyx mori mutant and is extracted from cocoons by autoclave. Porous sericin matrices are prepared by freeze dried method using genipin as crosslinker. The matrices are characterized biochemically and biophysically. The cell proliferation and viability of co-cultured fibroblasts and keratinocytes on matrices for at least 28 days are observed by live/dead assay, Alamar blue assay, and by dual fluorescent staining. The growth of the fibroblasts and keratinocytes in co-culture is correlated with the expression level of TGF-β, b-FGF and IL-8 in the cultured supernatants by enzyme-linked immunosorbent assay. The histological analysis further demonstrates a multi-layered stratified epidermal layer of uninhibited keratinocytes in co-cultured constructs. Presence of involucrin, collagen IV and the fibroblast surface protein in immuno-histochemical stained sections of co-cultured matrices indicates the significance of paracrine signaling between keratinocytes and fibroblasts in the expression of extracellular matrix protein for dermal repair. No significant amount of pro inflammatory cytokines (TNF-α, IL-1β and nitric oxide) production are evidenced when macrophages grown on the sericin matrices. The results all together depict the potentiality of sericin 3D matrices as skin equivalent tissue engineered construct in wound repair.

  10. Skin equivalent tissue-engineered construct: co-cultured fibroblasts/ keratinocytes on 3D matrices of sericin hope cocoons.

    Directory of Open Access Journals (Sweden)

    Sunita Nayak

    Full Text Available The development of effective and alternative tissue-engineered skin replacements to autografts, allografts and xenografts has became a clinical requirement due to the problems related to source of donor tissue and the perceived risk of disease transmission. In the present study 3D tissue engineered construct of sericin is developed using co-culture of keratinocytes on the upper surface of the fabricated matrices and with fibroblasts on lower surface. Sericin is obtained from "Sericin Hope" silkworm of Bombyx mori mutant and is extracted from cocoons by autoclave. Porous sericin matrices are prepared by freeze dried method using genipin as crosslinker. The matrices are characterized biochemically and biophysically. The cell proliferation and viability of co-cultured fibroblasts and keratinocytes on matrices for at least 28 days are observed by live/dead assay, Alamar blue assay, and by dual fluorescent staining. The growth of the fibroblasts and keratinocytes in co-culture is correlated with the expression level of TGF-β, b-FGF and IL-8 in the cultured supernatants by enzyme-linked immunosorbent assay. The histological analysis further demonstrates a multi-layered stratified epidermal layer of uninhibited keratinocytes in co-cultured constructs. Presence of involucrin, collagen IV and the fibroblast surface protein in immuno-histochemical stained sections of co-cultured matrices indicates the significance of paracrine signaling between keratinocytes and fibroblasts in the expression of extracellular matrix protein for dermal repair. No significant amount of pro inflammatory cytokines (TNF-α, IL-1β and nitric oxide production are evidenced when macrophages grown on the sericin matrices. The results all together depict the potentiality of sericin 3D matrices as skin equivalent tissue engineered construct in wound repair.

  11. Manufacturing of hydrogel biomaterials with controlled mechanical properties for tissue engineering applications.

    Science.gov (United States)

    Vedadghavami, Armin; Minooei, Farnaz; Mohammadi, Mohammad Hossein; Khetani, Sultan; Rezaei Kolahchi, Ahmad; Mashayekhan, Shohreh; Sanati-Nezhad, Amir

    2017-10-15

    Hydrogels have been recognized as crucial biomaterials in the field of tissue engineering, regenerative medicine, and drug delivery applications due to their specific characteristics. These biomaterials benefit from retaining a large amount of water, effective mass transfer, similarity to natural tissues and the ability to form different shapes. However, having relatively poor mechanical properties is a limiting factor associated with hydrogel biomaterials. Controlling the biomechanical properties of hydrogels is of paramount importance. In this work, firstly, mechanical characteristics of hydrogels and methods employed for characterizing these properties are explored. Subsequently, the most common approaches used for tuning mechanical properties of hydrogels including but are not limited to, interpenetrating polymer networks, nanocomposites, self-assembly techniques, and co-polymerization are discussed. The performance of different techniques used for tuning biomechanical properties of hydrogels is further compared. Such techniques involve lithography techniques for replication of tissues with complex mechanical profiles; microfluidic techniques applicable for generating gradients of mechanical properties in hydrogel biomaterials for engineering complex human tissues like intervertebral discs, osteochondral tissues, blood vessels and skin layers; and electrospinning techniques for synthesis of hybrid hydrogels and highly ordered fibers with tunable mechanical and biological properties. We finally discuss future perspectives and challenges for controlling biomimetic hydrogel materials possessing proper biomechanical properties. Hydrogels biomaterials are essential constituting components of engineered tissues with the applications in regenerative medicine and drug delivery. The mechanical properties of hydrogels play crucial roles in regulating the interactions between cells and extracellular matrix and directing the cells phenotype and genotype. Despite

  12. A bio-inspired swellable microneedle adhesive for mechanical interlocking with tissue

    Science.gov (United States)

    Yang, Seung Yun; O'Cearbhaill, Eoin D.; Sisk, Geoffroy C.; Park, Kyeng Min; Cho, Woo Kyung; Villiger, Martin; Bouma, Brett E.; Pomahac, Bohdan; Karp, Jeffrey M.

    2013-04-01

    Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here inspired by the endoparasite Pomphorhynchus laevis, which swells its proboscis to attach to its host’s intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~3.5-fold increase in adhesion strength compared with staples in skin graft fixation, and removal force of ~4.5 N cm-2 from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics.

  13. A Bio-Inspired Swellable Microneedle Adhesive for Mechanical Interlocking with Tissue

    Science.gov (United States)

    Yang, Seung Yun; O'Cearbhaill, Eoin D.; Sisk, Geoffroy C.; Park, Kyeng Min; Cho, Woo Kyung; Villiger, Martin; Bouma, Brett E.; Pomahac, Bohdan; Karp, Jeffrey M.

    2013-01-01

    Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here, inspired by the endoparasite Pomphorhynchus laevis which swells its proboscis to attach to its host’s intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~ 3.5 fold increase in adhesion strength compared to staples in skin graft fixation, and removal force of ~ 4.5 N/cm2 from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics. PMID:23591869

  14. A Robust Method to Generate Mechanically Anisotropic Vascular Smooth Muscle Cell Sheets for Vascular Tissue Engineering.

    Science.gov (United States)

    Backman, Daniel E; LeSavage, Bauer L; Shah, Shivem B; Wong, Joyce Y

    2017-06-01

    In arterial tissue engineering, mimicking native structure and mechanical properties is essential because compliance mismatch can lead to graft failure and further disease. With bottom-up tissue engineering approaches, designing tissue components with proper microscale mechanical properties is crucial to achieve the necessary macroscale properties in the final implant. This study develops a thermoresponsive cell culture platform for growing aligned vascular smooth muscle cell (VSMC) sheets by photografting N-isopropylacrylamide (NIPAAm) onto micropatterned poly(dimethysiloxane) (PDMS). The grafting process is experimentally and computationally optimized to produce PNIPAAm-PDMS substrates optimal for VSMC attachment. To allow long-term VSMC sheet culture and increase the rate of VSMC sheet formation, PNIPAAm-PDMS surfaces were further modified with 3-aminopropyltriethoxysilane yielding a robust, thermoresponsive cell culture platform for culturing VSMC sheets. VSMC cell sheets cultured on patterned thermoresponsive substrates exhibit cellular and collagen alignment in the direction of the micropattern. Mechanical characterization of patterned, single-layer VSMC sheets reveals increased stiffness in the aligned direction compared to the perpendicular direction whereas nonpatterned cell sheets exhibit no directional dependence. Structural and mechanical anisotropy of aligned, single-layer VSMC sheets makes this platform an attractive microstructural building block for engineering a vascular graft to match the in vivo mechanical properties of native arterial tissue. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. In vivo construction of tissue-engineered cartilage using adipose-derived stem cells and bioreactor technology.

    Science.gov (United States)

    Kang, Hongjun; Lu, Shibi; Peng, Jiang; Yang, Qiang; Liu, Shuyun; Zhang, Li; Huang, Jingxiang; Sui, Xiang; Zhao, Bin; Wang, Aiyuan; Xu, Wenjing; Guo, Quanyi; Song, Qing

    2015-03-01

    The present study aims to investigate the feasibility of tissue-engineered cartilage constructed in vivo and in vitro by dynamically culturing adipose-derived stem cells (ADSCs) with an articular cartilage acellular matrix in a bioreactor and subsequently implanting the cartilage in nude mice. ADSCs were proliferated, combined with three dimensional scaffolds (cell density: 5 × 10(7)/mL) and subsequently placed in a bioreactor and culture plate for 3 weeks. In the in vivo study, complexes cultured for 1 week under dynamic or static states were subcutaneously implanted into nude mice and collected after 3 weeks. Indicators such as gross morphology, histochemistry and immunohistochemistry were examined. In the in vitro study, histological observation showed that most scaffolds in the dynamic group were absorbed, and cell proliferation and matrix secretion were significant. Positive staining of safranin-O and alcian blue II collagen stain in the dynamic group was significantly stronger than that in the static culture group. In the in vivo study, cartilage-like tissues formed in the specimens of the two groups. Histological examination showed that cell distribution in the dynamic group was relatively more uniform than in the static group, and matrix secretion was relatively stronger. Bioreactor culturing can promote ADSC proliferation and cartilage differentiation and is thus a suitable method for constructing tissue-engineered cartilage in vivo.

  16. An overview of methods for the in vivo evaluation of tissue-engineered skin constructs

    NARCIS (Netherlands)

    Lammers, G.; Verhaegen, P.D.; Ulrich, M.M.; Schalkwijk, J.; Middelkoop, E.; Weiland, D.; Nillesen, S.T.M.; Kuppevelt, A.H.M.S.M. van; Daamen, W.F.

    2011-01-01

    Cutaneous wounding often leads to contraction and scarring, which may result in a range of functional, cosmetic, and psychological complications. Tissue-engineered skin substitutes are being developed to enhance restoration of the skin and improve the quality of wound healing. The aim of this review

  17. An Overview of Methods for the In Vivo Evaluation of Tissue-Engineered Skin Constructs

    NARCIS (Netherlands)

    Lammers, G.; Verhaegen, P.D.H.M.; Ulrich, M.; Schalkwijk, J.; Middelkoop, E.; Weiland, D.; Nillesen, S.T.M.; van Kuppevelt, T.H.; Daamen, W.F.

    2011-01-01

    Cutaneous wounding often leads to contraction and scarring, which may result in a range of functional, cosmetic, and psychological complications. Tissue-engineered skin substitutes are being developed to enhance restoration of the skin and improve the quality of wound healing. The aim of this review

  18. Endothelial cells assemble into a 3-dimensional prevascular network in a bone tissue engineering construct

    NARCIS (Netherlands)

    Rouwkema, Jeroen; de Boer, Jan; van Blitterswijk, Clemens

    2006-01-01

    To engineer tissues with clinically relevant dimensions, one must overcome the challenge of rapidly creating functional blood vessels to supply cells with oxygen and nutrients and to remove waste products. We tested the hypothesis that endothelial cells, cocultured with osteoprogenitor cells, can

  19. In-house Manual Construction of High-Density and High-Quality Tissue Microarrays by Using Homemade Recipient Agarose-Paraffin Blocks.

    Science.gov (United States)

    Kim, Kyu Ho; Choi, Suk Jin; Choi, Yeon Il; Kim, Lucia; Park, In Suh; Han, Jee Young; Kim, Joon Mee; Chu, Young Chae

    2013-06-01

    Self-made tissue punches can be effectively used to punch holes in blank recipient paraffin blocks and extract tissue cores from the donor paraffin blocks for the low-cost construction of tissue microarrays (TMAs). However, variable degrees of section distortion and loss of the tissue cores can occurs during cutting of the TMAs, posing technical problems for in-house manual construction of high-density TMAs. We aimed to update the method for in-house manual TMA construction to improve the quality of high-density TMAs. Blocks of agarose gel were subjected to the standard tissue processing and embedding procedure to prepare recipient agarose-paraffin blocks. The self-made tissue punches and recipient agarose-paraffin blocks were used to construct TMAs, which were completely melted and re-embedded in paraffin to make finished TMA blocks. The donor tissue cores were completely integrated into the surrounding paraffin of the recipient blocks. This method enabled us to construct high-density TMAs with significantly less section distortion or loss of tissue cores during microtomy. Simple and inexpensive construction of high-density and high-quality TMAs can be warranted by using paraffinized agarose gels as recipient blocks.

  20. The construction design of ball bearings used in the control rod driving mechanisms of PWRs

    International Nuclear Information System (INIS)

    Leng Chengmu; Huang Chongming; Chen Jianting.

    1986-01-01

    According to the operation conditions of ball bearings used in the control rod driving mechanisms of PWRs, this paper has analysed and discussed the problems that must be taken into account in the construction design of this ball bearing. It includes: a discussion about the reasonable selection of construction parameters of the bearing, deduction of the relationship between bearing clearance and contact angle, and the emphasis on the significance of assembling accuracy and torque measurement in the assurance of operational performance of the bearings. These experiences may be somewhat valuable for the design and application of this kind of ball bearing

  1. Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues

    Directory of Open Access Journals (Sweden)

    Hye-Sun Yu

    2016-02-01

    Full Text Available Mechanical loading is recognized to play an important role in regulating the behaviors of cells in bone and surrounding tissues in vivo. Many in vitro studies have been conducted to determine the effects of mechanical loading on individual cell types of the tissues. In this review, we focus specifically on the use of the Flexercell system as a tool for studying cellular responses to mechanical stretch. We assess the literature describing the impact of mechanical stretch on different cell types from bone, muscle, tendon, ligament, and cartilage, describing individual cell phenotype responses. In addition, we review evidence regarding the mechanotransduction pathways that are activated to potentiate these phenotype responses in different cell populations.

  2. Expression of glutathione transferases in corneal cell lines, corneal tissues and a human cornea construct.

    Science.gov (United States)

    Kölln, Christian; Reichl, Stephan

    2016-06-15

    Glutathione transferase (GST) expression and activity were examined in a three-dimensional human cornea construct and were compared to those of excised animal corneas. The objective of this study was to characterize phase II enzyme expression in the cornea construct with respect to its utility as an alternative to animal cornea models. The expression of the GSTO1-1 and GSTP1-1 enzymes was investigated using immunofluorescence staining and western blotting. The level of total glutathione transferase activity was determined using 1-chloro-2,4- dinitrobenzene as the substrate. Furthermore, the levels of GSTO1-1 and GSTP1-1 activity were examined using S-(4-nitrophenacyl)glutathione and ethacrynic acid, respectively, as the specific substrates. The expression and activity levels of these enzymes were examined in the epithelium, stroma and endothelium, the three main cellular layers of the cornea. In summary, the investigated enzymes were detected at both the protein and functional levels in the cornea construct and the excised animal corneas. However, the enzymatic activity levels of the human cornea construct were lower than those of the animal corneas. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Gelatin Scaffolds with Controlled Pore Structure and Mechanical Property for Cartilage Tissue Engineering.

    Science.gov (United States)

    Chen, Shangwu; Zhang, Qin; Nakamoto, Tomoko; Kawazoe, Naoki; Chen, Guoping

    2016-03-01

    Engineering of cartilage tissue in vitro using porous scaffolds and chondrocytes provides a promising approach for cartilage repair. However, nonuniform cell distribution and heterogeneous tissue formation together with weak mechanical property of in vitro engineered cartilage limit their clinical application. In this study, gelatin porous scaffolds with homogeneous and open pores were prepared using ice particulates and freeze-drying. The scaffolds were used to culture bovine articular chondrocytes to engineer cartilage tissue in vitro. The pore structure and mechanical property of gelatin scaffolds could be well controlled by using different ratios of ice particulates to gelatin solution and different concentrations of gelatin. Gelatin scaffolds prepared from ≥70% ice particulates enabled homogeneous seeding of bovine articular chondrocytes throughout the scaffolds and formation of homogeneous cartilage extracellular matrix. While soft scaffolds underwent cellular contraction, stiff scaffolds resisted cellular contraction and had significantly higher cell proliferation and synthesis of sulfated glycosaminoglycan. Compared with the gelatin scaffolds prepared without ice particulates, the gelatin scaffolds prepared with ice particulates facilitated formation of homogeneous cartilage tissue with significantly higher compressive modulus. The gelatin scaffolds with highly open pore structure and good mechanical property can be used to improve in vitro tissue-engineered cartilage.

  4. In vivo characterization of mechanical tissue properties of internal organs using endoscopic microscopy and inverse finite element analysis.

    Science.gov (United States)

    Schwenninger, David; Schumann, Stefan; Guttmann, Josef

    2011-02-03

    Knowledge about mechanical tissue properties is required for functional modelling and simulating of tissue and organ responses to external mechanical stress. To get the right properties especially for functional modelling of organs, tissue properties have to be determined in vivo. There are only few described methods for characterization of internal organ's tissue mechanics that can be applied in vivo. We introduce and evaluate a method to determine mechanical tissue properties, especially those of lung tissue, endoscopically. Inverse finite element analysis (utilizing a Neo-Hookean model for hyperelastic materials) and image processing algorithms are used to determine the shear modulus of a soft tissue. The resulting values for shear moduli were normally distributed. The shear modulus of the artificial tissue sample was determined with a relative error of 0.47% compared to the value obtained by uniaxial tensile test. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Statistical finite element method for real-time tissue mechanics analysis.

    Science.gov (United States)

    Mousavi, Seyed Reza; Khalaji, Iman; Sadeghi Naini, Ali; Raahemifar, Kaamran; Samani, Abbas

    2012-01-01

    The finite element (FE) method can accurately calculate tissue deformation. However, its low speed renders it ineffective for many biomedical applications involving real-time data processing. To accelerate FE analysis, we introduce a novel tissue mechanics simulation technique. This technique is suitable for real-time estimation of tissue deformation of specific organs, which is required in computer-aided diagnostic or therapeutic procedures. In this method, principal component analysis is used to describe each organ shape and its corresponding FE field for a pool of patients by a small number of weight factors. A mapping function is developed to relate the parameters of organ shape to their FE field counterpart. We show that irrespective of the complexity of the tissue's constitutive law or its loading conditions, the proposed technique is highly accurate and fast in estimating the FE field. Average deformation errors of less than 2% demonstrate the accuracy of the proposed technique.

  6. Mechanical characterization of intraluminal tissue with phase-resolved photoacoustic viscoelasticity endoscopy

    Science.gov (United States)

    Chen, Conggui; Zhao, Yue; Yang, Sihua; Xing, Da

    2015-01-01

    We developed a phase-sensitive side-scanning photoacoustic viscoelasticity endoscopy (PAVEE) for mechanical characterization of intraluminal tissues. In PAVEE, the PA phase can be extracted from the optical absorption induced ultrasonic waves and provides an index of viscoelasticity that is closely linked to tissue compositions. The transverse resolution of the PAVEE measured by carbon fiber was about 32 μm. The imaging capability of the PAVEE was verified using a vessel-mimicking phantom with different agar density. Moreover, PAVEE was investigated in processed lumen-shaped vascular tissues to evaluate the biomechanical features, which was highly consistent with the histology. The results demonstrated that the PAVEE can obtain viscoelastic properties of intraluminal tissues, which puts a new insight into the intravascular disease and holds great promise for plaque vulnerability detection. PMID:26713209

  7. Active Vertex Model for cell-resolution description of epithelial tissue mechanics.

    Directory of Open Access Journals (Sweden)

    Daniel L Barton

    2017-06-01

    Full Text Available We introduce an Active Vertex Model (AVM for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales. Furthermore, cell contacts are generated dynamically from positions of cell centres. This not only enables efficient numerical implementation, but provides a natural description of the T1 transition events responsible for local tissue rearrangements. The AVM also includes cell alignment, cell-specific mechanical properties, cell growth, division and apoptosis. In addition, the AVM introduces a flexible, dynamically changing boundary of the epithelial sheet allowing for studies of phenomena such as the fingering instability or wound healing. We illustrate these capabilities with a number of case studies.

  8. [Mechanical strength and mechano-compatibility of tissue-engineered bones].

    Science.gov (United States)

    Tanaka, Shigeo

    2016-01-01

    Current artificial bones made of metals and ceramics may be replaced around a decade after implantation due to its low durability, which is brought on by a large difference from the host bone in mechanical properties, i.e., low mechano-compatibility. On the other hand, tissue engineering could be a solution with regeneration of bone tissues from stem cells in vitro. However, there are still some problems to realize exactly the same mechanical properties as those of real bone. This paper introduces the technical background of bone tissue engineering and discusses possible methods for installation of mechano-compatibility into a regenerative bone. At the end, future directions toward the realization of ideal mechano-compatible regenerative bone are proposed.

  9. Active Vertex Model for cell-resolution description of epithelial tissue mechanics.

    Science.gov (United States)

    Barton, Daniel L; Henkes, Silke; Weijer, Cornelis J; Sknepnek, Rastko

    2017-06-01

    We introduce an Active Vertex Model (AVM) for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales. Furthermore, cell contacts are generated dynamically from positions of cell centres. This not only enables efficient numerical implementation, but provides a natural description of the T1 transition events responsible for local tissue rearrangements. The AVM also includes cell alignment, cell-specific mechanical properties, cell growth, division and apoptosis. In addition, the AVM introduces a flexible, dynamically changing boundary of the epithelial sheet allowing for studies of phenomena such as the fingering instability or wound healing. We illustrate these capabilities with a number of case studies.

  10. A mechanical design principle for tissue structure and function in the airway tree.

    Science.gov (United States)

    LaPrad, Adam S; Lutchen, Kenneth R; Suki, Béla

    2013-01-01

    With every breath, the dynamically changing mechanical pressures must work in unison with the cells and soft tissue structures of the lung to permit air to efficiently traverse the airway tree and undergo gas exchange in the alveoli. The influence of mechanics on cell and tissue function is becoming apparent, raising the question: how does the airway tree co-exist within its mechanical environment to maintain normal cell function throughout its branching structure of diminishing dimensions? We introduce a new mechanical design principle for the conducting airway tree in which mechanotransduction at the level of cells is driven to orchestrate airway wall structural changes that can best maintain a preferred mechanical microenvironment. To support this principle, we report in vitro radius-transmural pressure relations for a range of airway radii obtained from healthy bovine lungs and model the data using a strain energy function together with a thick-walled cylinder description. From this framework, we estimate circumferential stresses and incremental Young's moduli throughout the airway tree. Our results indicate that the conducting airways consistently operate within a preferred mechanical homeostatic state, termed mechanical homeostasis, that is characterized by a narrow range of circumferential stresses and Young's moduli. This mechanical homeostatic state is maintained for all airways throughout the tree via airway wall dimensional and mechanical relationships. As a consequence, cells within the airway walls throughout the airway tree experience similar oscillatory strains during breathing that are much smaller than previously thought. Finally, we discuss the potential implications of how the maintenance of mechanical homeostasis, while facilitating healthy tissue-level alterations necessary for maturation, may lead to airway wall structural changes capable of chronic asthma.

  11. Cellular Force Microscopy for in Vivo Measurements of Plant Tissue Mechanics1[W][OA

    Science.gov (United States)

    Routier-Kierzkowska, Anne-Lise; Weber, Alain; Kochova, Petra; Felekis, Dimitris; Nelson, Bradley J.; Kuhlemeier, Cris; Smith, Richard S.

    2012-01-01

    Although growth and morphogenesis are controlled by genetics, physical shape change in plant tissue results from a balance between cell wall loosening and intracellular pressure. Despite recent work demonstrating a role for mechanical signals in morphogenesis, precise measurement of mechanical properties at the individual cell level remains a technical challenge. To address this challenge, we have developed cellular force microscopy (CFM), which combines the versatility of classical microindentation techniques with the high automation and resolution approaching that of atomic force microscopy. CFM’s large range of forces provides the possibility to map the apparent stiffness of both plasmolyzed and turgid tissue as well as to perform micropuncture of cells using very high stresses. CFM experiments reveal that, within a tissue, local stiffness measurements can vary with the level of turgor pressure in an unexpected way. Altogether, our results highlight the importance of detailed physically based simulations for the interpretation of microindentation results. CFM’s ability to be used both to assess and manipulate tissue mechanics makes it a method of choice to unravel the feedbacks between mechanics, genetics, and morphogenesis. PMID:22353572

  12. On Constructing Dynamic and Forward Secure Authenticated Group Key Agreement Scheme from Multikey Encapsulation Mechanism.

    Science.gov (United States)

    Fathirad, Iraj; Devlin, John

    2015-01-01

    The approach of instantiating authenticated group key exchange (GAKE) protocol from the multikey encapsulation mechanism (mKEM) has an important advantage of achieving classical requirement of GAKE security in one communication round. In spite of the limitations of this approach, for example, lack of forward secrecy, it is very useful in group environments when maximum communication efficiency is desirable. To enrich this mKEM-based GAKE construction, we suggest an efficient solution to convert this static GAKE framework into a partially dynamic scheme. Furthermore, to address the associated lack of forward-secrecy, we propose two variants of this generic construction which can also provide a means of forward secrecy at the cost of extra communication round. In addition, concerning associated implementation cost of deploying this generic GAKE construction in elliptic curve cryptosystem, we compare the possible instantiations of this model from existing mKEM algorithms in terms of the number of elliptic curve scalar multiplications.

  13. A novel bioreactor to simulate urinary bladder mechanical properties and compliance for bladder functional tissue engineering.

    Science.gov (United States)

    Wei, Xin; Li, Dao-bing; Xu, Feng; Wang, Yan; Zhu, Yu-chun; Li, Hong; Wang, Kun-jie

    2011-02-01

    Bioreactors are pivotal tools for generating mechanical stimulation in functional tissue engineering study. This study aimed to create a bioreactor that can simulate urinary bladder mechanical properties, and to investigate the effects of a mechanically stimulated culture on urothelial cells and bladder smooth muscle cells. We designed a bioreactor to simulate the mechanical properties of bladder. A pressure-record system was used to evaluate the mechanical properties of the bioreactor by measuring the pressure in culture chambers. To test the biocompatibility of the bioreactor, viabilities of urothelial cells and smooth muscle cells cultured in the bioreactor under static and mechanically changed conditions were measured after 7-day culture. To evaluate the effect of mechanical stimulations on the vital cells, urethral cells and smooth muscle cells were cultured in the simulated mechanical conditions. After that, the viability and the distribution pattern of the cells were observed and compared with cells cultured in non-mechanical stimulated condition. The bioreactor system successfully generated waveforms similar to the intended programmed model while maintaining a cell-seeded elastic membrane between the chambers. There were no differences between viabilities of urothelial cells ((91.90 ± 1.22)% vs. (93.14 ± 1.78)%, P > 0.05) and bladder smooth muscle cells ((93.41 ± 1.49)% vs. (92.61 ± 1.34)%, P > 0.05). The viability of cells and tissue structure observation after cultured in simulated condition showed that mechanical stimulation was the only factor affected cells in the bioreactor and improved the arrangement of cells on silastic membrane. This bioreactor can effectively simulate the physiological and mechanical properties of the bladder. Mechanical stimulation is the only factor that affected the viability of cells cultured in the bioreactor. The bioreactor can change the growth behavior of urothelial cells and bladder smooth muscle cells, resulting in

  14. Construction of RNA-Seq libraries from large and microscopic tissues for the Illumina sequencing platform.

    Science.gov (United States)

    Atamian, Hagop S; Kaloshian, Isgouhi

    2012-01-01

    Second-generation DNA sequencing platforms have emerged as powerful tools in biological research. Their high sequence output at lower cost and minimal input DNA requirement render them suitable for broad applications ranging from gene expression studies to personalized clinical diagnostics. Here, we describe the preparation of cDNA libraries, from both whole aphid insects and their microscopic salivary gland tissues, suitable for high-throughput DNA sequencing on the Illumina platform.

  15. Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model

    Directory of Open Access Journals (Sweden)

    Alexandre Kaempfen

    2015-06-01

    Full Text Available The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step or only after six weeks of subcutaneous “incubation” (2-step. After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.

  16. Endothelial cells assemble into a 3-dimensional prevascular network in a bone tissue engineering construct.

    Science.gov (United States)

    Rouwkema, Jeroen; de Boer, Jan; Van Blitterswijk, Clemens A

    2006-09-01

    To engineer tissues with clinically relevant dimensions, one must overcome the challenge of rapidly creating functional blood vessels to supply cells with oxygen and nutrients and to remove waste products. We tested the hypothesis that endothelial cells, cocultured with osteoprogenitor cells, can organize into a prevascular network in vitro. When cultured in a spheroid coculture model with human mesenchymal stem cells, human umbilical vein endothelial cells (HUVECs) form a 3-dimensional prevascular network within 10 days of in vitro culture. The formation of the prevascular network was promoted by seeding 2% or fewer HUVECs. Moreover, the addition of endothelial cells resulted in a 4-fold upregulation of the osteogenic marker alkaline phosphatase. The addition of mouse embryonic fibroblasts did not result in stabilization of the prevascular network. Upon implantation, the prevascular network developed further and structures including lumen could be seen regularly. However, anastomosis with the host vasculature was limited. We conclude that endothelial cells are able to form a 3-dimensional (3D) prevascular network in vitro in a bone tissue engineering setting. This finding is a strong indication that in vitro prevascularization is a promising strategy to improve implant vascularization in bone tissue engineering.

  17. Construction of tissue compensating filters for extended areas in Hodgkin-irradiation on the basis of moire topography

    International Nuclear Information System (INIS)

    Binder, W.; Cabaj, A.; Kaercher, K.H.; Windischbauer, G.; Tieraerztliche Hochschule, Vienna

    1977-01-01

    In order to obtain a homogeneous distribution of the dose over extended fields in radiotherapy of Hodgkin's disease, for an exact dose within the irradiated region it is necessary to consider the topography of the patient. The skin protective build-up effect due to the use of bolus materials would be lost with telecobalt irradiation, and therefore tissue compensating filters with a large surface are to be preferred. A simple method of making such filters by means of the moire topography is described. The way to obtain a compensation filter for extended areas is demonstrated by an example showing how to construct it from layered lead plates. (orig./HP) [de

  18. Systemic Approach of a Virtual Enterprise that Constructs Wireless Payment Mechanisms

    Science.gov (United States)

    Assimakopoulos, Nikitas A.; Riggas, Anastasis N.; Kotsimpos, George K.

    2004-08-01

    Enterprises and Organizations are realizing that there are many win-win scenarios, for their customers and business partners, using the latest technology to enact convenient and secure purchases `over the air'. Wireless Payment (W/P) is the key element of Wireless Commerce. Businesses around the world are attempting to position themselves to operate in a highly competitive global economy. A single organization is often not able to develop sufficient internal design or production capabilities to respond effectively within a short period of time. The focus of this paper will be on the development and analysis of a Virtual Enterprise Architecture for the construction of W/P Mechanisms using Systemic Methodologies. A framework for the rapid and efficient integration of the business processes of the participating companies that construct W/P Mechanisms is provided.

  19. Dialogue on the threshold and diatribe: construction mechanisms of the individual's self-consciousness

    Directory of Open Access Journals (Sweden)

    Aurora Gedra Ruiz Alvarez

    2012-11-01

    Full Text Available This paper is about the dialogue on the threshold whose origins are in the Socratic dialogue and the diatribe (a dialogued internal gender, both understood as privileged mechanisms in the construction of the main character of Dostoevski´s novel Uma criatura dócil [The Meek One]. Its aim is to discuss the materiality of the text – mainly the dialogue on the threshold when the main character is in its existential crisis – and the mechanism of the diatribe which provokethe philosophical dialogue experience that the individual assumes while constituting his voice.

  20. Design, construction and performance evaluation of the target tissue thickness measurement system in intraoperative radiotherapy for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yazdani, Mohammad Reza, E-mail: myazdani@aut.ac.ir [Faculty of Energy Engineering and Physics, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Setayeshi, Saeed, E-mail: setayesh@aut.ac.ir [Faculty of Energy Engineering and Physics, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Arabalibeik, Hossein, E-mail: arabalibeik@tums.ac.ir [Research Center for Biomedical Technology and Robotics (RCBTR), Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Akbari, Mohammad Esmaeil [Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2017-05-21

    Intraoperative electron radiation therapy (IOERT), which uses electron beams for irradiating the target directly during the surgery, has the advantage of delivering a homogeneous dose to a controlled layer of tissue. Since the dose falls off quickly below the target thickness, the underlying normal tissues are spared. In selecting the appropriate electron energy, the accuracy of the target tissue thickness measurement is critical. In contrast to other procedures applied in IOERT, the routine measurement method is considered to be completely traditional and approximate. In this work, a novel mechanism is proposed for measuring the target tissue thickness with an acceptable level of accuracy. An electronic system has been designed and manufactured with the capability of measuring the tissue thickness based on the recorded electron density under the target. The results indicated the possibility of thickness measurement with a maximum error of 2 mm for 91.35% of data. Aside from system limitation in estimating the thickness of 5 mm phantom, for 88.94% of data, maximum error is 1 mm.

  1. Design, construction and performance evaluation of the target tissue thickness measurement system in intraoperative radiotherapy for breast cancer

    Science.gov (United States)

    Yazdani, Mohammad Reza; Setayeshi, Saeed; Arabalibeik, Hossein; Akbari, Mohammad Esmaeil

    2017-05-01

    Intraoperative electron radiation therapy (IOERT), which uses electron beams for irradiating the target directly during the surgery, has the advantage of delivering a homogeneous dose to a controlled layer of tissue. Since the dose falls off quickly below the target thickness, the underlying normal tissues are spared. In selecting the appropriate electron energy, the accuracy of the target tissue thickness measurement is critical. In contrast to other procedures applied in IOERT, the routine measurement method is considered to be completely traditional and approximate. In this work, a novel mechanism is proposed for measuring the target tissue thickness with an acceptable level of accuracy. An electronic system has been designed and manufactured with the capability of measuring the tissue thickness based on the recorded electron density under the target. The results indicated the possibility of thickness measurement with a maximum error of 2 mm for 91.35% of data. Aside from system limitation in estimating the thickness of 5 mm phantom, for 88.94% of data, maximum error is 1 mm.

  2. Dynamic Mechanical Compression of Chondrocytes for Tissue Engineering: A Critical Review.

    Science.gov (United States)

    Anderson, Devon E; Johnstone, Brian

    2017-01-01

    Articular cartilage functions to transmit and translate loads. In a classical structure-function relationship, the tissue resides in a dynamic mechanical environment that drives the formation of a highly organized tissue architecture suited to its biomechanical role. The dynamic mechanical environment includes multiaxial compressive and shear strains as well as hydrostatic and osmotic pressures. As the mechanical environment is known to modulate cell fate and influence tissue development toward a defined architecture in situ , dynamic mechanical loading has been hypothesized to induce the structure-function relationship during attempts at in vitro regeneration of articular cartilage. Researchers have designed increasingly sophisticated bioreactors with dynamic mechanical regimes, but the response of chondrocytes to dynamic compression and shear loading remains poorly characterized due to wide variation in study design, system variables, and outcome measurements. We assessed the literature pertaining to the use of dynamic compressive bioreactors for in vitro generation of cartilaginous tissue from primary and expanded chondrocytes. We used specific search terms to identify relevant publications from the PubMed database and manually sorted the data. It was very challenging to find consensus between studies because of species, age, cell source, and culture differences, coupled with the many loading regimes and the types of analyses used. Early studies that evaluated the response of primary bovine chondrocytes within hydrogels, and that employed dynamic single-axis compression with physiologic loading parameters, reported consistently favorable responses at the tissue level, with upregulation of biochemical synthesis and biomechanical properties. However, they rarely assessed the cellular response with gene expression or mechanotransduction pathway analyses. Later studies that employed increasingly sophisticated biomaterial-based systems, cells derived from different

  3. An empirical look at the Defense Mechanism Test (DMT): reliability and construct validity.

    Science.gov (United States)

    Ekehammar, Bo; Zuber, Irena; Konstenius, Marja-Liisa

    2005-07-01

    Although the Defense Mechanism Test (DMT) has been in use for almost half a century, there are still quite contradictory views about whether it is a reliable instrument, and if so, what it really measures. Thus, based on data from 39 female students, we first examined DMT inter-coder reliability by analyzing the agreement among trained judges in their coding of the same DMT protocols. Second, we constructed a "parallel" photographic picture that retained all structural characteristic of the original and analyzed DMT parallel-test reliability. Third, we examined the construct validity of the DMT by (a) employing three self-report defense-mechanism inventories and analyzing the intercorrelations between DMT defense scores and corresponding defenses in these instruments, (b) studying the relationships between DMT responses and scores on trait and state anxiety, and (c) relating DMT-defense scores to measures of self-esteem. The main results showed that the DMT can be coded with high reliability by trained coders, that the parallel-test reliability is unsatisfactory compared to traditional psychometric standards, that there is a certain generalizability in the number of perceptual distortions that people display from one picture to another, and that the construct validation provided meager empirical evidence for the conclusion that the DMT measures what it purports to measure, that is, psychological defense mechanisms.

  4. Mathematical Modeling of Uniaxial Mechanical Properties of Collagen Gel Scaffolds for Vascular Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Ramiro M. Irastorza

    2015-01-01

    Full Text Available Small diameter tissue-engineered arteries improve their mechanical and functional properties when they are mechanically stimulated. Applying a suitable stress and/or strain with or without a cycle to the scaffolds and cells during the culturing process resides in our ability to generate a suitable mechanical model. Collagen gel is one of the most used scaffolds in vascular tissue engineering, mainly because it is the principal constituent of the extracellular matrix for vascular cells in human. The mechanical modeling of such a material is not a trivial task, mainly for its viscoelastic nature. Computational and experimental methods for developing a suitable model for collagen gels are of primary importance for the field. In this research, we focused on mechanical properties of collagen gels under unconfined compression. First, mechanical viscoelastic models are discussed and framed in the control system theory. Second, models are fitted using system identification. Several models are evaluated and two nonlinear models are proposed: Mooney-Rivlin inspired and Hammerstein models. The results suggest that Mooney-Rivlin and Hammerstein models succeed in describing the mechanical behavior of collagen gels for cyclic tests on scaffolds (with best fitting parameters 58.3% and 75.8%, resp.. When Akaike criterion is used, the best is the Mooney-Rivlin inspired model.

  5. Mathematical modeling of uniaxial mechanical properties of collagen gel scaffolds for vascular tissue engineering.

    Science.gov (United States)

    Irastorza, Ramiro M; Drouin, Bernard; Blangino, Eugenia; Mantovani, Diego

    2015-01-01

    Small diameter tissue-engineered arteries improve their mechanical and functional properties when they are mechanically stimulated. Applying a suitable stress and/or strain with or without a cycle to the scaffolds and cells during the culturing process resides in our ability to generate a suitable mechanical model. Collagen gel is one of the most used scaffolds in vascular tissue engineering, mainly because it is the principal constituent of the extracellular matrix for vascular cells in human. The mechanical modeling of such a material is not a trivial task, mainly for its viscoelastic nature. Computational and experimental methods for developing a suitable model for collagen gels are of primary importance for the field. In this research, we focused on mechanical properties of collagen gels under unconfined compression. First, mechanical viscoelastic models are discussed and framed in the control system theory. Second, models are fitted using system identification. Several models are evaluated and two nonlinear models are proposed: Mooney-Rivlin inspired and Hammerstein models. The results suggest that Mooney-Rivlin and Hammerstein models succeed in describing the mechanical behavior of collagen gels for cyclic tests on scaffolds (with best fitting parameters 58.3% and 75.8%, resp.). When Akaike criterion is used, the best is the Mooney-Rivlin inspired model.

  6. Mechanical Characterization of Tissue-Engineered Cartilage Using Microscopic Magnetic Resonance Elastography

    Science.gov (United States)

    Yin, Ziying; Schmid, Thomas M.; Yasar, Temel K.; Liu, Yifei; Royston, Thomas J.

    2014-01-01

    Knowledge of mechanical properties of tissue-engineered cartilage is essential for the optimization of cartilage tissue engineering strategies. Microscopic magnetic resonance elastography (μMRE) is a recently developed MR-based technique that can nondestructively visualize shear wave motion. From the observed wave pattern in MR phase images the tissue mechanical properties (e.g., shear modulus or stiffness) can be extracted. For quantification of the dynamic shear properties of small and stiff tissue-engineered cartilage, μMRE needs to be performed at frequencies in the kilohertz range. However, at frequencies greater than 1 kHz shear waves are rapidly attenuated in soft tissues. In this study μMRE, with geometric focusing, was used to overcome the rapid wave attenuation at high frequencies, enabling the measurement of the shear modulus of tissue-engineered cartilage. This methodology was first tested at a frequency of 5 kHz using a model system composed of alginate beads embedded in agarose, and then applied to evaluate extracellular matrix development in a chondrocyte pellet over a 3-week culture period. The shear stiffness in the pellet was found to increase over time (from 6.4 to 16.4 kPa), and the increase was correlated with both the proteoglycan content and the collagen content of the chondrocyte pellets (R2=0.776 and 0.724, respectively). Our study demonstrates that μMRE when performed with geometric focusing can be used to calculate and map the shear properties within tissue-engineered cartilage during its development. PMID:24266395

  7. Interleukin-6 blockade attenuates lung cancer tissue construction integrated by cancer stem cells.

    Science.gov (United States)

    Ogawa, Hiroyuki; Koyanagi-Aoi, Michiyo; Otani, Kyoko; Zen, Yoh; Maniwa, Yoshimasa; Aoi, Takashi

    2017-09-26

    In the present study, we successfully generated lung cancer stem cell (CSC)-like cells by introducing a small set of transcription factors into a lung cancer cell line. In addition to properties that are conventionally referred to as CSC properties, the lung induced CSCs exhibited the ability to form lung cancer-like tissues in vitro with vascular cells and mesenchymal stem cells, which showed structures and immunohistological patterns that were similar to human lung cancer tissues. We named them "lung cancer organoids". We found that interleukin-6 (IL-6), which was expressed in the lung induced CSCs, facilitates the formation of lung cancer organoids via the conversion of mesenchymal stem cells into alpha-smooth muscle actin (αSMA)-positive cells. Interestingly, the combination of anti-IL-6 antibody and cisplatin could destroy the lung cancer organoids, while cisplatin alone could not. Furthermore, IL-6 mRNA-positive cancer cells were found in clinical lung cancer samples. These results suggest that IL-6 could be a novel therapeutic target in lung cancer.

  8. Modelling the mechanics of partially mineralized collagen fibrils, fibres and tissue

    Science.gov (United States)

    Liu, Yanxin; Thomopoulos, Stavros; Chen, Changqing; Birman, Victor; Buehler, Markus J.; Genin, Guy M.

    2014-01-01

    Progressive stiffening of collagen tissue by bioapatite mineral is important physiologically, but the details of this stiffening are uncertain. Unresolved questions about the details of the accommodation of bioapatite within and upon collagen's hierarchical structure have posed a central hurdle, but recent microscopy data resolve several major questions. These data suggest how collagen accommodates bioapatite at the lowest relevant hierarchical level (collagen fibrils), and suggest several possibilities for the progressive accommodation of bioapatite at higher hierarchical length scales (fibres and tissue). We developed approximations for the stiffening of collagen across spatial hierarchies based upon these data, and connected models across hierarchies levels to estimate mineralization-dependent tissue-level mechanics. In the five possible sequences of mineralization studied, percolation of the bioapatite phase proved to be an important determinant of the degree of stiffening by bioapatite. The models were applied to study one important instance of partially mineralized tissue, which occurs at the attachment of tendon to bone. All sequences of mineralization considered reproduced experimental observations of a region of tissue between tendon and bone that is more compliant than either tendon or bone, but the size and nature of this region depended strongly upon the sequence of mineralization. These models and observations have implications for engineered tissue scaffolds at the attachment of tendon to bone, bone development and graded biomimetic attachment of dissimilar hierarchical materials in general. PMID:24352669

  9. Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism

    Directory of Open Access Journals (Sweden)

    Agathi-Vasiliki Goula

    2013-07-01

    Full Text Available More than fifteen genetic diseases, including Huntington’s disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease progression. DNA damage and base excision repair (BER are involved in repeat instability and might contribute to the tissue selectivity of the process. In this review, we will discuss the mechanisms of trinucleotide repeat instability, focusing more specifically on the role of BER.

  10. Capabilities and Limitations of Tissue Size Control through Passive Mechanical Forces.

    Directory of Open Access Journals (Sweden)

    Jochen Kursawe

    2015-12-01

    Full Text Available Embryogenesis is an extraordinarily robust process, exhibiting the ability to control tissue size and repair patterning defects in the face of environmental and genetic perturbations. The size and shape of a developing tissue is a function of the number and size of its constituent cells as well as their geometric packing. How these cellular properties are coordinated at the tissue level to ensure developmental robustness remains a mystery; understanding this process requires studying multiple concurrent processes that make up morphogenesis, including the spatial patterning of cell fates and apoptosis, as well as cell intercalations. In this work, we develop a computational model that aims to understand aspects of the robust pattern repair mechanisms of the Drosophila embryonic epidermal tissues. Size control in this system has previously been shown to rely on the regulation of apoptosis rather than proliferation; however, to date little work has been done to understand the role of cellular mechanics in this process. We employ a vertex model of an embryonic segment to test hypotheses about the emergence of this size control. Comparing the model to previously published data across wild type and genetic perturbations, we show that passive mechanical forces suffice to explain the observed size control in the posterior (P compartment of a segment. However, observed asymmetries in cell death frequencies across the segment are demonstrated to require patterning of cellular properties in the model. Finally, we show that distinct forms of mechanical regulation in the model may be distinguished by differences in cell shapes in the P compartment, as quantified through experimentally accessible summary statistics, as well as by the tissue recoil after laser ablation experiments.

  11. Evaluation of ionizing radiation effects in bone tissue by FTIR spectroscopy and dynamic mechanical analysis

    International Nuclear Information System (INIS)

    Veloso, Marcelo N.; Santin, Stefany P.; Benetti, Carolina; Pereira, Thiago M.; Mattor, Monica B.; Politano, Rodolfo; Zezell, Denise M.

    2013-01-01

    In many medical practices the bone tissue exposure to ionizing radiation is necessary. However, this radiation can interact with bone tissue in a molecular level, causing chemical and mechanical changes related with the dose used. The aim of this study was verify the changes promoted by different doses of ionizing radiation in bone tissue using spectroscopy technique of Attenuate Total Reflectance - Fourier Transforms Infrared (ATR-FTIR) and dynamic mechanical analysis. Samples of bovine bone were irradiated using irradiator of Cobalt-60 with five different doses between 0.01 kGy, 0.1 kGy,1 kGy, 15 kGy and 75 kGy. To study the effects of ionizing irradiation on bone chemical structure the sub-bands of amide I and the crystallinity index were studied. The mechanical changes were evaluated using the elastic modulus and the damping value. To verify if the chemical changes and the bone mechanic characteristics were related, it was made one study about the correlation between the crystallinity index and the elastic modulus, between the sub-bands ratio and the damping value and between the sub-bands ratio and the elastic modulus. It was possible to evaluate the effects of different dose of ionizing radiation in bone tissue. With ATR-FTIR spectroscopy analysis, it was possible observe changes in the organic components and in the hydroxyapatite crystals organization. Changes were also observed in the mechanical properties. A good correlation between the techniques was found, however, it was not possible to establish a linear or exponential dependence between dose and effect. (author)

  12. Construction and characterization of a cDNA library from liver tissue of Chinese Banna minipig inbred line.

    Science.gov (United States)

    Tan, W; Chen, Y; Zhang, L; Lu, Y; Li, S; Zeng, R; Zeng, Y; Li, Y; Cheng, J

    2006-09-01

    A xenograft that performs efficient functions is an essential premise for successful xenotransplantation. Our early study indicated that Chinese Banna minipig inbred line (BMI) was an ideal xenograft donor. However, the activities of some proteins synthesized by the BMI liver are different from the human, which could lead to functional disorders in coagulation, fibrinolysis, and anticoagulation after liver xenotransplantation. Therefore, it is important to investigate the genetic background of protein incompatibility and to provide new strategies for gene manipulation. In this study we constructed a cDNA expression library using BMI liver tissue to obtain an understanding of nucleic acid and protein differences between the two species. We extracted total RNA and purified mRNA of the liver tissue from one of the sixteenth inbred generation of BMI/JS 151 substrain. After double-strand cDNA synthesis, we fractionated it on a CHROMA APIN-400 column; ligated the longer than 500bp cDNA into a ZAP Express Vector; and performed a lambda: phage packaging reaction, library amplification, and titer. We randomly picked 12 plaques and tested the length of inserts. The titers of the primary and amplified libraries were 1.0 x 10(6) pfu/mL and 5.0 x 10(9) pfu/mL, respectively. The percentages of recombinants were 97.0% in the primary library and 98.0% in the amplified library. The lengths of most inserts were between 750 bp and 2.0 kb. Thus, we successfully constructed a cDNA expression library from BMI liver tissue. Using the library, we hope to get a full-length cDNA of some important genes and conduct further studies on porcine liver function in xenotransplantation.

  13. Active tension network model suggests an exotic mechanical state realized in epithelial tissues

    Science.gov (United States)

    Noll, Nicholas; Mani, Madhav; Heemskerk, Idse; Streichan, Sebastian J.; Shraiman, Boris I.

    2017-12-01

    Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behaviour remains an open problem. Here we formulate and analyse the active tension network (ATN) model, which assumes that the mechanical balance of cells within a tissue is dominated by cortical tension and introduces tension-dependent active remodelling of the cortex. We find that ATNs exhibit unusual mechanical properties. Specifically, an ATN behaves as a fluid at short times, but at long times supports external tension like a solid. Furthermore, an ATN has an extensively degenerate equilibrium mechanical state associated with a discrete conformal--`isogonal'--deformation of cells. The ATN model predicts a constraint on equilibrium cell geometries, which we demonstrate to approximately hold in certain epithelial tissues. We further show that isogonal modes are observed in the fruit fly embryo, accounting for the striking variability of apical areas of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, the study of which helps to understand biological phenomena.

  14. Mathematical model for osteobstruction in bone regeneration mechanisms: a headway in skeletal tissue engineering.

    Science.gov (United States)

    Ogunsalu, C; Arunaye, F I; Ezeokoli, C; Gardner, M; Rohrer, M; Prasad, H

    2012-11-01

    In this paper, we formulate a mathematical model for the evaluation of parameters responsible for the retardation and eventual acceleration of bone regeneration on the contralateral side of the mandible of experimental animals, following the discovery of a new mechanism of bone regeneration called the osteobstruction mechanism (a negative mechanism of bone regeneration as opposed to the well established and extensively documented positive mechanisms such as osteogenesis, osteoinduction and osteoconduction). This osteobstructive mechanism was demonstrated by episodes of overtaking and reovertaking on single photon emission computed tomography (SPECT) following evaluation of osteoblastic activities in a sequential animal experiment to validate both the Ogunsalu sandwich technique (a double guided tissue technique; D-GTR) and the interceed membrane technique (a single guided tissue regeneration technique; S-GTR) utilizing SPECT, histological and histomorphometric evaluation. This work is now given special attention in terms of mathematical analysis because of limited experimental observations since experiments cannot be observed infinitely. Mathematical modelling is as such essential to generalize the results of this osteobstructive mechanism in bone regeneration. We utilize the Fisher's equation to describe bone cell mobilization during bone regeneration by two different techniques: the Ogunsalu sandwich bone regeneration technique (D-GTR) and the S-GTR.

  15. Methods of Assessing Human Tendon Metabolism and Tissue Properties in Response to Changes in Mechanical Loading

    DEFF Research Database (Denmark)

    Heinemeier, Katja M; Kjaer, Michael; Magnusson, S Peter

    2016-01-01

    expression as well as protein synthesis rate. Further the (14)C bomb-pulse method has provided data on long-term tissue turnover in human tendon. Non-invasive techniques allow measurement of tendon metabolism (positron emission tomography (PET)), tendon morphology (magnetic resonance imaging (MRI......In recent years a number of methodological developments have improved the opportunities to study human tendon. Microdialysis enables sampling of interstitial fluid in the peritendon tissue, while sampling of human tendon biopsies allows direct analysis of tendon tissue for gene- and protein......)), and tendon mechanical properties (ultrasonography combined with force measurement during movement). Finally, 3D cell cultures of human tendon cells provide the opportunity to investigate cell-matrix interactions in response to various interventions....

  16. Construction and selection of lifting-based multiwavelets for mechanical fault detection

    Science.gov (United States)

    Yuan, Jing; He, Zhengjia; Zi, Yanyang; Wei, Ying

    2013-11-01

    The essence of wavelet transforms is a similar measurement between the signal and the wavelet basis functions. Thus, the construction and selection of the proper wavelet basis functions similar to the fault feature and possessing good properties such as vanishing moments have vital importance to the effective fault diagnosis. In this paper, the construction of lifting-based adaptive multiwavelets with various vanishing moments and the selection rules for different mechanical fault detection are proposed. On the basis of the fixed cubic Hermite multiwavelets, lifting schemes are adopted to construct new changeable multiwavelets with diverse vanishing moments. Then, the defined local spectral entropy minimization rules are proposed to determine the optimum multiwavelets providing the proper vanishing moments, classified into the typical shaft faults, gear faults and rolling bearing faults. The proposed method is applied to incipient fault diagnosis of rolling bearing and gearbox fault diagnosis of rolling mill to verify its effectiveness and feasibility in comparison with different wavelet transforms and spectral kurtosis. The results show that the proposed method can act as a promising tool for mechanical fault detection.

  17. Regeneration of skull bones in adult rabbits after implantation of commercial osteoinductive materials and transplantation of a tissue-engineering construct.

    Science.gov (United States)

    Volkov, A V; Alekseeva, I S; Kulakov, A A; Gol'dshtein, D V; Shustrov, S A; Shuraev, A I; Arutyunyan, I V; Bukharova, T B; Rzhaninova, A A; Bol'shakova, G B; Grigor'yan, A S

    2010-10-01

    We performed a comparative study of reparative osteogenesis in rabbits with experimental critical defects of the parietal bones after implantation of commercial osteoinductive materials "Biomatrix", "Osteomatrix", "BioOss" in combination with platelet-rich plasma and transplantation of a tissue-engineering construct on the basis of autogenic multipotent stromal cells from the adipose tissue predifferentiated in osteogenic direction. It was found that experimental reparative osteogenesis is insufficiently stimulated by implantation materials and full-thickness trepanation holes were not completely closed. After transplantation of the studied tissue-engineering construct, the defect was filled with full-length bone regenerate (in the center of the regenerate and from the maternal bone) in contrast to control and reference groups, where the bone tissue was formed only on the side of the maternal bone. On day 120 after transplantation of the tissue-engineering construct, the percent of newly-formed bone tissue in the regenerate was 24% (the total percent of bone tissue in the regenerate was 39%), which attested to active incomplete regenerative process in contrast to control and reference groups. Thus, the study demonstrated effective regeneration of the critical defects of the parietal bones in rabbits 120 days after transplantation of the tissue-engineering construct in contrast to commercial osteoplastic materials for directed bone regeneration.

  18. Finite element analysis, mechanical assessment and material comparison of two volar slab constructs.

    Science.gov (United States)

    Hamilton, Steven W; Aboud, Hussain

    2009-04-01

    In order to help prevent joint stiffness, the injured or postoperative hand is splinted in the intrinsic-plus position. We aimed to determine the strongest type of volar slab construct that would be appropriate in this treatment. Two constructs were compared, a double-ridged and a non-ridged slab. Two materials were used, plaster of Paris (POP) and resin. We performed finite element analysis (FEA) and mechanical assessment to establish which combination of construct and material resulted in the strongest volar slab. We were unable to form ridges on the resin slab, and therefore this construct was not tested. Finite element analysis showed that most stress occurred at the wrist region, where all the slabs failed. The double-ridged POP slab was found to be 5.3 times stronger than the non-ridged POP slab and 1.4 times stronger than the non-ridged resin slab (pslab, we suggest forming two anterior ridges in the plaster.

  19. Mechanisms of foot-and-mouth disease virus tropism inferred from differential tissue gene expression.

    Directory of Open Access Journals (Sweden)

    James J Zhu

    Full Text Available Foot-and-mouth disease virus (FMDV targets specific tissues for primary infection, secondary high-titer replication (e.g. foot and mouth where it causes typical vesicular lesions and long-term persistence at some primary replication sites. Although integrin αVβ6 receptor has been identified as primary FMDV receptors in animals, their tissue distribution alone fails to explain these highly selective tropism-driven events. Thus, other molecular mechanisms must play roles in determining this tissue specificity. We hypothesized that differences in certain biological activities due to differential gene expression determine FMDV tropism and applied whole genome gene expression profiling to identify genes differentially expressed between FMDV-targeted and non-targeted tissues in terms of supporting primary infection, secondary replication including vesicular lesions, and persistence. Using statistical and bioinformatic tools to analyze the differential gene expression, we identified mechanisms that could explain FMDV tissue tropism based on its association with differential expression of integrin αVβ6 heterodimeric receptor (FMDV receptor, fibronectin (ligand of the receptor, IL-1 cytokines, death receptors and the ligands, and multiple genes in the biological pathways involved in extracellular matrix turnover and interferon signaling found in this study. Our results together with reported findings indicate that differences in (1 FMDV receptor availability and accessibility, (2 type I interferon-inducible immune response, and (3 ability to clear virus infected cells via death receptor signaling play roles in determining FMDV tissue tropism and the additional increase of high extracellular matrix turnover induced by FMDV infection, likely via triggering the signaling of highly expressed IL-1 cytokines, play a key role in the pathogenesis of vesicular lesions.

  20. Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives

    Science.gov (United States)

    Sanz-Herrera, Jose A.; Reina-Romo, Esther

    2011-01-01

    Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle) levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields. PMID:22174660

  1. Fabrication and mechanical characterization of 3D electrospun scaffolds for tissue engineering

    International Nuclear Information System (INIS)

    Wright, L D; Young, R T; Andric, T; Freeman, J W

    2010-01-01

    Electrospinning is a polymer processing technique that produces fibrous structures comparable to the extracellular matrix of many tissues. Electrospinning, however, has been severely limited in its tissue engineering capabilities because this technique has produced few three-dimensional structures. Sintering of electrospun materials provides a method to fabricate unique architectures and allow much larger structures to be made. Electrospun mats were sintered into strips and cylinders, and their tensile and compressive mechanical properties were measured. In addition, electrospun materials with salt pores (salt embedded within the material and then leached out) were fabricated to improve porosity of the electrospun materials for tissue engineering scaffolds. Sintered electrospun poly(d,l-lactide) and poly(l-lactide) (PDLA/PLLA) materials have higher tensile mechanical properties (modulus: 72.3 MPa, yield: 960 kPa) compared to unsintered PLLA (modulus: 40.36 MPa, yield: 675.5 kPa). Electrospun PDLA/PLLA cylinders with and without salt-leached pores had compressive moduli of 6.69 and 26.86 MPa, respectively, and compressive yields of 1.36 and 0.56 MPa, respectively. Sintering of electrospun materials is a novel technique that improves electrospinning application in tissue engineering by increasing the size and types of electrospun structures that can be fabricated.

  2. Regulatory mechanism and research progress of connective tissue growth factor in diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Xi-Da Liang

    2016-04-01

    Full Text Available Diabetic retinopathy is one of the microvascular abnormal diseases. In the late stage of disease progression, the antibody of vascular endothelial growth factor can significantly inhibit the formation of new blood vessels and improve macular edema, which is widely used in clinical. However, the aggravation of pro-fibrotic influence after long-term treated by the medicine also attracts a wide range of attention. Connective tissue growth factor, as an important cytokine in intraocular fibrosis, over expressed after treated by the drug, is considered to be one of the most important factors in the side effect of the drug, and is also a potential therapeutic target. After finishing the current research, the regulation mechanism of connective tissue growth factor, includes two ways, regulation of gene expression and direct binding to other cell factors or receptors. Because of its special four module structure, it has many kinds of cell factor specific binding sites, and its regulation mode is more dependent on the latter, which promotes or inhibits the expression of several important cytokine pathways. In diabetic retinopathy, its expression goes throughout the disease process. The accumulation of connective tissue growth factor plays an important role in promoting the thickening of basement membrane and the formation of new blood vessels in the early stage of the clinical stage and the formation of the new blood vessels. In this paper, the regulatory mechanism of connective tissue growth factor and the research progress of this factor in DR are systematically expounded.

  3. A Pulsatile Bioreactor for Conditioning of Tissue-Engineered Cardiovascular Constructs under Endoscopic Visualization

    Directory of Open Access Journals (Sweden)

    Bassil Akra

    2012-07-01

    Full Text Available Heart valve disease (HVD is a globally increasing problem and accounts for thousands of deaths yearly. Currently end-stage HVD can only be treated by total valve replacement, however with major drawbacks. To overcome the limitations of conventional substitutes, a new clinical approach based on cell colonization of artificially manufactured heart valves has been developed. Even though this attempt seems promising, a confluent and stable cell layer has not yet been achieved due to the high stresses present in this area of the human heart. This study describes a bioreactor with a new approach to cell conditioning of tissue engineered heart valves. The bioreactor provides a low pulsatile flow that grants the correct opening and closing of the valve without high shear stresses. The flow rate can be regulated allowing a steady and sensitive conditioning process. Furthermore, the correct functioning of the valve can be monitored by endoscope surveillance in real-time. The tubeless and modular design allows an accurate, simple and faultless assembly of the reactor in a laminar flow chamber. It can be concluded that the bioreactor provides a strong tool for dynamic pre-conditioning and monitoring of colonized heart valve prostheses physiologically exposed to shear stress.

  4. Molecular mechanism of hypoxia-induced chondrogenesis and its application in in vivo cartilage tissue engineering.

    OpenAIRE

    Duval , Elise; Baugé , Catherine; Andriamanalijaona , Rina; Bénateau , Hervé; Leclercq , Sylvain; Dutoit , Soizic; Poulain , Laurent; Galéra , Philippe; Boumédiene , Karim

    2012-01-01

    International audience; Cartilage engineering is one of the most challenging issue in regenerative medicine, due to its limited self-ability to repair. Here, we assessed engineering of cartilage tissue starting from human bone marrow (hBM) stem cells under hypoxic environment and delineated the mechanism whereby chondrogenesis could be conducted without addition of exogenous growth factors. hBM stem cells were cultured in alginate beads and chondrogenesis was monitored by chondrocyte phenotyp...

  5. Dynamic mechanical response of brain tissue in indentation in vivo, in situ and in vitro.

    Science.gov (United States)

    Prevost, Thibault P; Jin, Guang; de Moya, Marc A; Alam, Hasan B; Suresh, Subra; Socrate, Simona

    2011-12-01

    Characterizing the dynamic mechanical properties of brain tissue is deemed important for developing a comprehensive knowledge of the mechanisms underlying brain injury. The results gathered to date on the tissue properties have been mostly obtained in vitro. Learning how these results might differ quantitatively from those encountered in vivo is a critical step towards the development of biofidelic brain models. The present study provides novel and unique experimental results on, and insights into, brain biorheology in vivo, in situ and in vitro, at large deformations, in the quasi-static and dynamic regimes. The nonlinear dynamic response of the cerebral cortex was measured in indentation on the exposed frontal and parietal lobes of anesthetized porcine subjects. Load-unload cycles were applied to the tissue surface at sinusoidal frequencies of 10, 1, 0.1 and 0.01 Hz. Ramp-relaxation tests were also conducted to assess the tissue viscoelastic behavior at longer times. After euthanasia, the indentation test sequences were repeated in situ on the exposed cortex maintained in its native configuration within the cranium. Mixed gray and white matter samples were subsequently excised from the superior cortex to be subjected to identical indentation test segments in vitro within 6-7 h post mortem. The main response features (e.g. nonlinearities, rate dependencies, hysteresis and conditioning) were measured and contrasted in vivo, in situ and in vitro. The indentation response was found to be significantly stiffer in situ than in vivo. The consistent, quantitative set of mechanical measurements thereby collected provides a preliminary experimental database, which may be used to support the development of constitutive models for the study of mechanically mediated pathways leading to traumatic brain injury. Copyright © 2011 Acta Materialia Inc. All rights reserved.

  6. Mechanical Stretching Promotes Skin Tissue Regeneration via Enhancing Mesenchymal Stem Cell Homing and Transdifferentiation.

    Science.gov (United States)

    Liang, Xiao; Huang, Xiaolu; Zhou, Yiwen; Jin, Rui; Li, Qingfeng

    2016-07-01

    Skin tissue expansion is a clinical procedure for skin regeneration to reconstruct cutaneous defects that can be accompanied by severe complications. The transplantation of mesenchymal stem cells (MSCs) has been proven effective in promoting skin expansion and helping to ameliorate complications; however, systematic understanding of its mechanism remains unclear. MSCs from luciferase-Tg Lewis rats were intravenously transplanted into a rat tissue expansion model to identify homing and transdifferentiation. To clarify underlying mechanisms, a systematic approach was used to identify the differentially expressed genes between mechanically stretched human MSCs and controls. The biological significance of these changes was analyzed through bioinformatic methods. We further investigated genes and pathways of interest to disclose their potential role in mechanical stretching-induced skin regeneration. Cross sections of skin samples from the expanded group showed significantly more luciferase(+) and stromal cell-derived factor 1α (SDF-1α)(+), luciferase(+)keratin 14(+), and luciferase(+)CD31(+) cells than the control group, indicating MSC transdifferentiation into epidermal basal cells and endothelial cells after SDF-1α-mediated homing. Microarray analysis suggested upregulation of genes related to hypoxia, vascularization, and cell proliferation in the stretched human MSCs. Further investigation showed that the homing of MSCs was blocked by short interfering RNA targeted against matrix metalloproteinase 2, and that mechanical stretching-induced vascular endothelial growth factor A upregulation was related to the Janus kinase/signal transducer and activator of transcription (Jak-STAT) and Wnt signaling pathways. This study determines that mechanical stretching might promote skin regeneration by upregulating MSC expression of genes related to hypoxia, vascularization, and cell proliferation; enhancing transplanted MSC homing to the expanded skin; and

  7. Tissue heterogeneity as a mechanism for localized neural stimulation by applied electric fields

    International Nuclear Information System (INIS)

    Miranda, P C; Correia, L; Salvador, R; Basser, P J

    2007-01-01

    We investigate the heterogeneity of electrical conductivity as a new mechanism to stimulate excitable tissues via applied electric fields. In particular, we show that stimulation of axons crossing internal boundaries can occur at boundaries where the electric conductivity of the volume conductor changes abruptly. The effectiveness of this and other stimulation mechanisms was compared by means of models and computer simulations in the context of transcranial magnetic stimulation. While, for a given stimulation intensity, the largest membrane depolarization occurred where an axon terminates or bends sharply in a high electric field region, a slightly smaller membrane depolarization, still sufficient to generate action potentials, also occurred at an internal boundary where the conductivity jumped from 0.143 S m -1 to 0.333 S m -1 , simulating a white-matter-grey-matter interface. Tissue heterogeneity can also give rise to local electric field gradients that are considerably stronger and more focal than those impressed by the stimulation coil and that can affect the membrane potential, albeit to a lesser extent than the two mechanisms mentioned above. Tissue heterogeneity may play an important role in electric and magnetic 'far-field' stimulation

  8. Development of Chitosan Scaffolds with Enhanced Mechanical Properties for Intestinal Tissue Engineering Applications.

    Science.gov (United States)

    Zakhem, Elie; Bitar, Khalil N

    2015-10-13

    Massive resections of segments of the gastrointestinal (GI) tract lead to intestinal discontinuity. Functional tubular replacements are needed. Different scaffolds were designed for intestinal tissue engineering application. However, none of the studies have evaluated the mechanical properties of the scaffolds. We have previously shown the biocompatibility of chitosan as a natural material in intestinal tissue engineering. Our scaffolds demonstrated weak mechanical properties. In this study, we enhanced the mechanical strength of the scaffolds with the use of chitosan fibers. Chitosan fibers were circumferentially-aligned around the tubular chitosan scaffolds either from the luminal side or from the outer side or both. Tensile strength, tensile strain, and Young's modulus were significantly increased in the scaffolds with fibers when compared with scaffolds without fibers. Burst pressure was also increased. The biocompatibility of the scaffolds was maintained as demonstrated by the adhesion of smooth muscle cells around the different kinds of scaffolds. The chitosan scaffolds with fibers provided a better candidate for intestinal tissue engineering. The novelty of this study was in the design of the fibers in a specific alignment and their incorporation within the scaffolds.

  9. Engineering the mechanical and biological properties of nanofibrous vascular grafts for in situ vascular tissue engineering.

    Science.gov (United States)

    Henry, Jeffrey J D; Yu, Jian; Wang, Aijun; Lee, Randall; Fang, Jun; Li, Song

    2017-08-17

    Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.

  10. The mechanics of hyaluronic acid/adipic acid dihydrazide hydrogel: towards developing a vessel for delivery of preadipocytes to native tissues.

    Science.gov (United States)

    Shoham, Naama; Sasson, Aviad Levi; Lin, Feng-Huei; Benayahu, Dafna; Haj-Ali, Rami; Gefen, Amit

    2013-12-01

    Promising treatment approaches in repairing tissue defects include implementation of regenerative medicine strategies, particularly delivery of preadipocytes to sites where adipose tissue damage needs to be repaired or where fat needs to be generated. In this study, we suggest that the injectable hyaluronic acid/adipic acid dihydrazide (HA/ADH) hydrogel may be an adipose-tissue-like material in terms of biological compatibility as well as mechanical behavior. First, we show that the hydrogel enables and supports growth, proliferation and differentiation of 3T3-L1 preadipocytes. Second, given that adipose tissue is a weight-bearing biological structure, we investigate the large deformation mechanical behavior of the hydrogel with and without embedded preadipocytes, by performing confined and unconfined compression tests and then calibrating a strain energy density (SED) function to the results. Four test groups were examined: (1) Hydrogel specimens right after the preparation without cells, (2) and (3) 3-days-cultured hydrogel specimens with and without cells, respectively, and (4) 6-days-cultured hydrogel specimens with cells. A one-term Ogden SED was found to adequately describe the hyperelastic behavior of the hydrogel specimens in all experimental groups. Importantly, we found that the mechanical properties of the hydrogel, when subjected to compression, are in good agreement with those of native adipose tissue, with the better fit occurring 3-6 days after preparation of the hydrogel. Third, computational finite element studies of the mechanical (stress-strain) behavior of the HA/ADH hydrogel when containing mature adipocytes indicated that the stiffnesses of the constructs were mildly affected by the presence of the adipocytes. Hence, we conclude that injectable HA/ADH hydrogel may serve as a vessel for protecting preadipocytes during, and at a short-term after delivery to native tissues, e.g. in research towards regenerative medicine in tissue reconstructions

  11. Effect of well construction on the mechanical state of unconsolidated methane hydrate-bearing sediment

    Science.gov (United States)

    Sasaki, T.; Soga, K.; Yamamoto, K.

    2016-12-01

    World's first offshore production of gas from methane hydrate-bearing sediment was accomplished in Nankai Trough off the coast of Japan. The achievement signals the beginning of exploitation of methane hydrate as a new source of energy, as an estimated amount of the new gas resource significantly exceeds that of the existing conventional oil and gas resources. Conventional gas reservoirs exist in consolidated sediment (i.e. rocks) thousands of metres below seafloor, and such sediment is hard enough to resist deformation. Methane hydrate reservoirs, on the other hand, lies only a couple of hundreds of metres down the seafloor, which means the sediment is unconsolidated (i.e. soils) and is readily deformed. In addition, the hydrate melts away in the pore space when it releases gas, giving rise to a significant rearrangement of stresses in the sediment. Well construction in methane hydrate reservoir might affect the mechanical state of the sediment to the point where the interpretation of the fracture pressure test becomes difficult and sand production could be enhanced. Existing numerical simulations tend to overlook soil mechanics, which is more appropriate than rock mechanics to model unconsolidated sediment, and the effect of methane hydrate on soil's mechanical behaviour is missed. In the present research, the construction of well in unconsolidated hydrate-bearing sediment was modelled with finite element analysis incorporating the critical state soil mechanics. Results showed that cement shrinkage in the well annulus would have a significant effect on the principal stresses and directions of the sediment even if the magnitude of the shrinkage was 0.1%. Cement shrinkage would also promote the generation of plastic strains, potentially enhancing sand production. Results also showed that the direction of fracture inferred from a fracture pressure test at Nankai Trough might have been vertical, indicating it was developed at the cement-sediment interface.

  12. Acellular ostrich corneal stroma used as scaffold for construction of tissue-engineered cornea

    Directory of Open Access Journals (Sweden)

    Xian-Ning Liu

    2016-03-01

    Full Text Available AIM: To assess acellular ostrich corneal matrix used as a scaffold to reconstruct a damaged cornea. METHODS: A hypertonic saline solution combined with a digestion method was used to decellularize the ostrich cornea. The microstructure of the acellular corneal matrix was observed by transmission electron microscopy (TEM and hematoxylin and eosin (H&E staining. The mechanical properties were detected by a rheometer and a tension machine. The acellular corneal matrix was also transplanted into a rabbit cornea and cytokeratin 3 was used to check the immune phenotype. RESULTS: The microstructure and mechanical properties of the ostrich cornea were well preserved after the decellularization process. In vitro, the methyl thiazolyl tetrazolium results revealed that extracts of the acellular ostrich corneas (AOCs had no inhibitory effects on the proliferation of the corneal epithelial or endothelial cells or on the keratocytes. The rabbit lamellar keratoplasty showed that the transplanted AOCs were transparent and completely incorporated into the host cornea while corneal turbidity and graft dissolution occurred in the acellular porcine cornea (APC transplantation. The phenotype of the reconstructed cornea was similar to a normal rabbit cornea with a high expression of cytokeratin 3 in the superficial epithelial cell layer. CONCLUSION: We first used AOCs as scaffolds to reconstruct damaged corneas. Compared with porcine corneas, the anatomical structures of ostrich corneas are closer to those of human corneas. In accordance with the principle that structure determines function, a xenograft lamellar keratoplasty also confirmed that the AOC transplantation generated a superior outcome compared to that of the APC graft.

  13. Research on Mechanical Properties of Concrete Constructs Based on Terrestrial Laser Scanning Measurement

    Directory of Open Access Journals (Sweden)

    Hao Yang

    2016-05-01

    Full Text Available Terrestrial laser scanning (TLS technology is broadly accepted as a structural health monitoring device for reinforced concrete (RC composite structures. Both experiments and numerical analysis are considered. In this submit, measurements were conducted for the composite concrete beams. The emphasis in numerical simulation is given on finite element methods (FEM which is corrected by the response surface methodology (RSM. Aspects considered are effects of material parameters and variation in geometry. This paper describes our recent progress on FEM modeling of damages in concrete composite structures based on the TLS measurement. We also focus on the research about mechanical properties of concrete constructs here.

  14. In Vitro Mineralization of an Osteoid-Like Dense Collagen Construct for Bone Tissue Engineering

    Science.gov (United States)

    Marelli, Benedetto

    -seeded constructs. In conclusion, since the role of the collagen framework microstructure on its mineralization has been previously ignored, the present doctoral dissertation provides new insights into collagen mineralization. More significantly, since collagen matrices are difficult to mineralize in vivo, and need to be taken out of physiological boundaries to effect in vitro mineralization, it is predicted that this work will have a significant impact on the production of rapidly implantable and mineralizable constructs for bone regenerative therapy. (Abstract shortened by UMI.)

  15. Chitosan fibers with improved biological and mechanical properties for tissue engineering applications.

    Science.gov (United States)

    Albanna, Mohammad Z; Bou-Akl, Therese H; Blowytsky, Oksana; Walters, Henry L; Matthew, Howard W T

    2013-04-01

    The low mechanical properties of hydrogel materials such as chitosan hinder their broad utility for tissue engineering applications. Previous research efforts improved the mechanical properties of chitosan fiber through chemical and physical modifications; however, unfavorable toxicity effects on cells were reported. In this paper, we report the preparation of chitosan fibers with improved mechanical and biocompatibility properties. The structure-property relationships of extruded chitosan fibers were explored by varying acetic acid (AA) concentration, ammonia concentration, annealing temperature and degree of heparin crosslinking. Results showed that optimizing AA concentration to 2vol% improved fiber strength and stiffness by 2-fold. Extruding chitosan solution into 25wt% of ammonia solution reduced fiber diameters and improved fiber strength by 2-fold and stiffness by 3-fold, due to an increase in crystallinity as confirmed by XRD. Fiber annealing further reduced fiber diameter and improved fiber strength and stiffness as temperature increased. Chitosan fibers crosslinked with heparin had increased diameter but lower strength and stiffness properties and higher breaking strain values. When individual parameters were combined, further improvement in fiber mechanical properties was achieved. All mechanically improved fibers and heparin crosslinked fibers promoted valvular interstitial cells (VIC) attachment and growth over 10 day cultures. Our results demonstrate the ability to substantially improve the mechanical properties of chitosan fibers without adversely affecting their biological properties. The investigated treatments offer numerous advantages over previous physical/chemical modifications and thus are expected to expand the utility of chitosan fibers with tunable mechanical properties in various tissue engineering applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Contribution of collagen and elastin fibers to the mechanical behavior of an abdominal connective tissue.

    Science.gov (United States)

    Levillain, A; Orhant, M; Turquier, F; Hoc, T

    2016-08-01

    The linea alba is a complex structure commonly involved in hernia formation. Knowledge of its mechanical behavior is essential to design suitable meshes and reduce the risk of recurrence. The aim of this study was to investigate the relationships between the mechanical properties of the linea alba and the organization of collagen and elastin fibers. For that purpose, longitudinal and transversal samples were removed from four porcine and three human linea alba, to perform tensile tests under a biphotonic confocal microscope, in each direction. Microscopic observation revealed a tissue composed of two layers, made of transversal collagen fibers in the dorsal side and oblique collagen fibers in the ventral side. This particular architecture led to an anisotropic mechanical behavior, with higher stress in the transversal direction. During loading, oblique fibers of the ventral layer reoriented toward the tensile axis in both directions, while fibers of the dorsal layer remained in the transversal direction. This rotation of oblique fibers progressively increased the stiffness of the tissue and induced a non-linear stress-stretch relation. Elastin fibers formed a layer covering the collagen fibers and followed their movement, suggesting that they ensure their elastic recoil. All of these results demonstrated the strong relationships between the microstructure and the mechanical behavior of the linea alba. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Multi-scale mechanical response of freeze-dried collagen scaffolds for tissue engineering applications.

    Science.gov (United States)

    Offeddu, Giovanni S; Ashworth, Jennifer C; Cameron, Ruth E; Oyen, Michelle L

    2015-02-01

    Tissue engineering has grown in the past two decades as a promising solution to unresolved clinical problems such as osteoarthritis. The mechanical response of tissue engineering scaffolds is one of the factors determining their use in applications such as cartilage and bone repair. The relationship between the structural and intrinsic mechanical properties of the scaffolds was the object of this study, with the ultimate aim of understanding the stiffness of the substrate that adhered cells experience, and its link to the bulk mechanical properties. Freeze-dried type I collagen porous scaffolds made with varying slurry concentrations and pore sizes were tested in a viscoelastic framework by macroindentation. Membranes made up of stacks of pore walls were indented using colloidal probe atomic force microscopy. It was found that the bulk scaffold mechanical response varied with collagen concentration in the slurry consistent with previous studies on these materials. Hydration of the scaffolds resulted in a more compliant response, yet lesser viscoelastic relaxation. Indentation of the membranes suggested that the material making up the pore walls remains unchanged between conditions, so that the stiffness of the scaffolds at the scale of seeded cells is unchanged; rather, it is suggested that thicker pore walls or more of these result in the increased moduli for the greater slurry concentration conditions. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Coping as a Multifaceted Construct: Associations With Psychological Outcomes Among Family Members of Mechanical Ventilation Survivors.

    Science.gov (United States)

    Nadig, Nandita; Huff, Nidhi G; Cox, Christopher E; Ford, Dee W

    2016-09-01

    To develop and evaluate a preliminary multifaceted model for coping among family members of patients who survive mechanical ventilation. In this multicenter cross-sectional survey, we interviewed family members of mechanically ventilated patients at the time of transfer from the ICU to the hospital ward. We constructed a theoretic model of coping that included characteristics attributable to family members, family-clinician rapport, and patients. We then explored relationships between coping factors and symptoms of psychological distress (anxiety, depression, and posttraumatic stress). Fifty-six family members of survivors of mechanical ventilation. Psychological distress measured by the Hospital Anxiety and Depression Scale and Posttraumatic Stress Scale. Optimism measured using the Life Orientation Test scale, resiliency by Conner-Davidson Resilience Scale, and social support using the Patient Reported Outcomes Measurement Information System inventory. Family members had moderate levels of psychological distress with median total Hospital Anxiety and Depression Scale equal to 14 (interquartile range, 5-20) and Posttraumatic Stress Scale equal to 22 (interquartile range, 15-31). Among family member characteristics, greater optimism (p = 0.001, Hospital Anxiety and Depression Scale; p = 0.010, Posttraumatic Stress Scale), resilience (p = 0.012, Hospital Anxiety and Depression Scale), and social support (p = 0.013, Hospital Anxiety and Depression Scale) were protective against psychological distress. On the contrary, characteristics of family-clinician rapport such as communication quality and presence of conflict did not have any associations with psychological distress. To our knowledge, this is the first study to explore coping as a multifaceted construct and its relationship with family psychological outcomes among survivors of mechanical ventilation. We found certain family characteristics of coping such as optimism, resilience, and social support to be

  19. The implementation of clean development mechanism (CDM) in the construction and built environment industry

    International Nuclear Information System (INIS)

    Mok, Ken L.; Han, Seung H.; Choi, Seokjin

    2014-01-01

    Greenhouse gas emissions due to human activities are the main contributors to global climate change, a problem that should not be ignored. Through the clean development mechanism (CDM) introduced under the Kyoto Protocol, developing countries are able to earn certified emission reduction (CER) credits through a myriad of emission reduction projects. This study aims to explore the potential of implementing CDM projects in the construction and built environment (C and BE) industry, which has been criticized for not only consuming an enormous amount of resources, but also for contributing to adverse environmental health. In this research, we limit the boundary of the C and BE industry to include the planning, procurement, construction, occupation and refurbishment/demolition phases of a project's life cycle. Surveys and in-depth follow-up interviews with experts have generated useful insights pertaining to CDM potential and its adaptation into the C and BE industry. From this foundation, this paper evaluates the current obstacles to CDM and presents feasible suggestions to increase CDM projects related to the C and BE industry. - Highlights: • We review the development and limitation of CDM relates to the construction and built environment (C and BE) industry. • We obtain experts' opinions on the feasibility of CDM in the C and BE industry. • Validation, monitoring, verification and additionality of CDM projects are crucial. • Experts agreed that most of our suggestions are feasible in principle

  20. Mix design and mechanical performance of geopolymer binder for sustainable construction and building material

    Science.gov (United States)

    Saeli, Manfredi; Novais, Rui M.; Seabra, Maria Paula; Labrincha, João A.

    2017-11-01

    Sustainability in construction is a major concern worldwide, due to the huge volume of materials and energy consumed by this sector. Associated supplementing industries (e.g. Portland cement production) constitute a significant source of CO2 emissions and global warming. Valorisation and reuse of industrial wastes and by-products make geopolymers a solid and sustainable via to be followed as a valid alternative to Portland cement. In this work the mix design of a green fly ash-based geopolymer is evaluated as an environmentally friendly construction material. In the pursuit of sustainability, wastes from a regional kraft pulp industry are exploited for the material processing. Furthermore, a simple, reproducible, and low-cost manufacture is used. The mix design is hence optimised in order to improve the desirable mechanical performance of the material intended for structural applications in construction. Tests indicate that geopolymers may efficiently substitute the ordinary Portland cement as a mortar/concrete binder. Furthermore, valorisation and reuse of wastes in geopolymers is a suboptimal way of gaining financial surplus for the involved industrial players, while contributes for the implementation of a desirable circular economy.

  1. Tissue engineering of cartilage using a mechanobioreactor exerting simultaneous mechanical shear and compression to simulate the rolling action of articular joints.

    Science.gov (United States)

    Shahin, Kifah; Doran, Pauline M

    2012-04-01

    The effect of dynamic mechanical shear and compression on the synthesis of human tissue-engineered cartilage was investigated using a mechanobioreactor capable of simulating the rolling action of articular joints in a mixed fluid environment. Human chondrocytes seeded into polyglycolic acid (PGA) mesh or PGA-alginate scaffolds were precultured in shaking T-flasks or recirculation perfusion bioreactors for 2.5 or 4 weeks prior to mechanical stimulation in the mechanobioreactor. Constructs were subjected to intermittent unconfined shear and compressive loading at a frequency of 0.05 Hz using a peak-to-peak compressive strain amplitude of 2.2% superimposed on a static axial compressive strain of 6.5%. The mechanical treatment was carried out for up to 2.5 weeks using a loading regime of 10 min duration each day with the direction of the shear forces reversed after 5 min and release of all loading at the end of the daily treatment period. Compared with shaking T-flasks and mechanobioreactor control cultures without loading, mechanical treatment improved the amount and quality of cartilage produced. On a per cell basis, synthesis of both major structural components of cartilage, glycosaminoglycan (GAG) and collagen type II, was enhanced substantially by up to 5.3- and 10-fold, respectively, depending on the scaffold type and seeding cell density. Levels of collagen type II as a percentage of total collagen were also increased after mechanical treatment by up to 3.4-fold in PGA constructs. Mechanical treatment had a less pronounced effect on the composition of constructs precultured in perfusion bioreactors compared with perfusion culture controls. This work demonstrates that the quality of tissue-engineered cartilage can be enhanced significantly by application of simultaneous dynamic mechanical shear and compression, with the greatest benefits evident for synthesis of collagen type II. Copyright © 2011 Wiley Periodicals, Inc.

  2. In vivo periodontal tissue regeneration by periodontal ligament stem cells and endothelial cells in three-dimensional cell sheet constructs.

    Science.gov (United States)

    Panduwawala, C P; Zhan, X; Dissanayaka, W L; Samaranayake, L P; Jin, L; Zhang, C

    2017-06-01

    Chronic periodontitis causes damage to tooth-supporting tissues, resulting in tooth loss in adults. Recently, cell-sheet-based approaches have been studied to overcome the limitations of conventional cytotherapeutic procedures for periodontal regeneration. The purpose of the present study was to investigate the regenerative potential of periodontal ligament stem cells (PDLSCs) and human umbilical vein endothelial cells (HUVECs) in three-dimensional (3D) cell sheet constructs for periodontal regeneration in vivo. PDLSCs, HUVECs or co-cultures of both cells were seeded onto temperature-responsive culture dishes, and intact cell sheets were fabricated. Cell sheets were wrapped around the prepared human roots in three different combinations and implanted subcutaneously into immunodeficient mice. Histological evaluation revealed that after 2, 4 and 8 wk of implantation, periodontal ligament-like tissue arrangements were observed around the implanted roots in experimental groups compared with controls. Vascular lumens were also observed in periodontal compartments of HUVEC-containing groups. Periodontal ligament regeneration, cementogenesis and osteogenesis were evident in the experimental groups at both weeks 4 and 8, as shown by immunostaining for periostin and bone sialoprotein. Human cells in the transplanted cell sheets were stained by immunohistochemistry for the presence of human mitochondria. The 3D cell sheet-based approach may be potentially beneficial and is thus encouraged for future regenerative periodontal therapy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. A structural model for the flexural mechanics of nonwoven tissue engineering scaffolds.

    Science.gov (United States)

    Engelmayr, George C; Sacks, Michael S

    2006-08-01

    The development of methods to predict the strength and stiffness of biomaterials used in tissue engineering is critical for load-bearing applications in which the essential functional requirements are primarily mechanical. We previously quantified changes in the effective stiffness (E) of needled nonwoven polyglycolic acid (PGA) and poly-L-lactic acid (PLLA) scaffolds due to tissue formation and scaffold degradation under three-point bending. Toward predicting these changes, we present a structural model for E of a needled nonwoven scaffold in flexure. The model accounted for the number and orientation of fibers within a representative volume element of the scaffold demarcated by the needling process. The spring-like effective stiffness of the curved fibers was calculated using the sinusoidal fiber shapes. Structural and mechanical properties of PGA and PLLA fibers and PGA, PLLA, and 50:50 PGA/PLLA scaffolds were measured and compared with model predictions. To verify the general predictive capability, the predicted dependence of E on fiber diameter was compared with experimental measurements. Needled nonwoven scaffolds were found to exhibit distinct preferred (PD) and cross-preferred (XD) fiber directions, with an E ratio (PD/XD) of approximately 3:1. The good agreement between the predicted and experimental dependence of E on fiber diameter (R2 = 0.987) suggests that the structural model can be used to design scaffolds with E values more similar to native soft tissues. A comparison with previous results for cell-seeded scaffolds (Engelmayr, G. C., Jr., et al., 2005, Biomaterials, 26(2), pp. 175-187) suggests, for the first time, that the primary mechanical effect of collagen deposition is an increase in the number of fiber-fiber bond points yielding effectively stiffer scaffold fibers. This finding indicated that the effects of tissue deposition on needled nonwoven scaffold mechanics do not follow a rule-of-mixtures behavior. These important results underscore

  4. Mechanical enhancement and in vitro biocompatibility of nanofibrous collagen-chitosan scaffolds for tissue engineering.

    Science.gov (United States)

    Zou, Fengjuan; Li, Runrun; Jiang, Jianjun; Mo, Xiumei; Gu, Guofeng; Guo, Zhongwu; Chen, Zonggang

    2017-12-01

    The collagen-chitosan complex with a three-dimensional nanofiber structure was fabricated to mimic native ECM for tissue repair and biomedical applications. Though the three-dimensional hierarchical fibrous structures of collagen-chitosan composites could provide more adequate stimulus to facilitate cell adhesion, migrate and proliferation, and thus have the potential as tissue engineering scaffolding, there are still limitations in their applications due to the insufficient mechanical properties of natural materials. Because poly (vinyl alcohol) (PVA) and thermoplastic polyurethane (TPU) as biocompatible synthetic polymers can offer excellent mechanical properties, they were introduced into the collagen-chitosan composites to fabricate the mixed collagen/chitosan/PVA fibers and a sandwich structure (collagen/chitosan-TPU-collagen/chitosan) of nanofiber in order to enhance the mechanical properties of the nanofibrous collagen-chitosan scaffold. The results showed that the tensile behavior of materials was enhanced to different degrees with the difference of collagen content in the fibers. Besides the Young's modulus had no obvious changes, both the break strength and the break elongation of materials were heightened after reinforced by PVA. For the collagen-chitosan nanofiber reinforced by TPU, both the break strength and the Young's modulus of materials were heightened in different degrees with the variety of collagen content in the fibers despite the decrease of the break elongation of materials to some extent. In vitro cell test demonstrated that the materials could provide adequate environment for cell adhesion and proliferation. All these indicated that the reinforced collagen-chitosan nanofiber could be as potential scaffold for tissue engineering according to the different mechanical requirements in clinic.

  5. Construction of a preclinical multimodality phantom using tissue-mimicking materials for quality assurance in tumor size measurement.

    Science.gov (United States)

    Lee, Yongsook C; Fullerton, Gary D; Goins, Beth A

    2013-07-29

    World Health Organization (WHO) and the Response Evaluation Criteria in Solid Tumors (RECIST) working groups advocated standardized criteria for radiologic assessment of solid tumors in response to anti-tumor drug therapy in the 1980s and 1990s, respectively. WHO criteria measure solid tumors in two-dimensions, whereas RECIST measurements use only one-dimension which is considered to be more reproducible (1, 2, 3,4,5). These criteria have been widely used as the only imaging biomarker approved by the United States Food and Drug Administration (FDA) (6). In order to measure tumor response to anti-tumor drugs on images with accuracy, therefore, a robust quality assurance (QA) procedures and corresponding QA phantom are needed. To address this need, the authors constructed a preclinical multimodality (for ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI)) phantom using tissue-mimicking (TM) materials based on the limited number of target lesions required by RECIST by revising a Gammex US commercial phantom (7). The Appendix in Lee et al. demonstrates the procedures of phantom fabrication (7). In this article, all protocols are introduced in a step-by-step fashion beginning with procedures for preparing the silicone molds for casting tumor-simulating test objects in the phantom, followed by preparation of TM materials for multimodality imaging, and finally construction of the preclinical multimodality QA phantom. The primary purpose of this paper is to provide the protocols to allow anyone interested in independently constructing a phantom for their own projects. QA procedures for tumor size measurement, and RECIST, WHO and volume measurement results of test objects made at multiple institutions using this QA phantom are shown in detail in Lee et al. (8).

  6. Mechanical properties of cocoons constructed consecutively by a single silkworm caterpillar, Bombyx mori

    Science.gov (United States)

    Huang, S. Q.; Zhao, H. P.; Feng, X. Q.; Cui, W.; Lin, Z.; Xu, M. Q.

    2008-04-01

    Most animals have the ability to adapt, to some extends and in different ways, the variation or disturbance of environment. In our experiments, we forced a silkworm caterpillar to spin two, three or four thin cocoons by taking it out from the cocoon being constructed. The mechanical properties of these cocoons were studied by static tensile tests and dynamic mechanical thermal analysis. Though external disturbances may cause the decrease in the total weight of silk spun by the silkworm, a gradual enhancement was interestingly found in the mechanical properties of these thin cocoons. Scanning electron microscopy observations of the fractured specimens of the cocoons showed that there exist several different energy dissipation mechanisms occurred simultaneously at macro-, meso-, and micro-scales, yielding a superior capacity of cocoons to adsorb the energy of possible attacks from the outside and to protect efficiently its pupa against damage. Through evolution of millions of years, therefore, the silkworm Bombyx mori seems to have gained the ability to adapt external disturbances and to redesign a new cocoon with optimized protective function when its first cocoon has been damaged for some reasons.

  7. Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

    Science.gov (United States)

    Khozoee, Baktash; Mafi, Pouya; Mafi, Reza; Khan, Wasim S

    2017-01-01

    Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Mechanical stimulation of mesenchymal stem cells: Implications for cartilage tissue engineering.

    Science.gov (United States)

    Fahy, Niamh; Alini, Mauro; Stoddart, Martin J

    2018-01-01

    Articular cartilage is a load-bearing tissue playing a crucial mechanical role in diarthrodial joints, facilitating joint articulation, and minimizing wear. The significance of biomechanical stimuli in the development of cartilage and maintenance of chondrocyte phenotype in adult tissues has been well documented. Furthermore, dysregulated loading is associated with cartilage pathology highlighting the importance of mechanical cues in cartilage homeostasis. The repair of damaged articular cartilage resulting from trauma or degenerative joint disease poses a major challenge due to a low intrinsic capacity of cartilage for self-renewal, attributable to its avascular nature. Bone marrow-derived mesenchymal stem cells (MSCs) are considered a promising cell type for cartilage replacement strategies due to their chondrogenic differentiation potential. Chondrogenesis of MSCs is influenced not only by biological factors but also by the environment itself, and various efforts to date have focused on harnessing biomechanics to enhance chondrogenic differentiation of MSCs. Furthermore, recapitulating mechanical cues associated with cartilage development and homeostasis in vivo, may facilitate the development of a cellular phenotype resembling native articular cartilage. The goal of this review is to summarize current literature examining the effect of mechanical cues on cartilage homeostasis, disease, and MSC chondrogenesis. The role of biological factors produced by MSCs in response to mechanical loading will also be examined. An in-depth understanding of the impact of mechanical stimulation on the chondrogenic differentiation of MSCs in terms of endogenous bioactive factor production and signaling pathways involved, may identify therapeutic targets and facilitate the development of more robust strategies for cartilage replacement using MSCs. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:52-63, 2018. © 2017 Orthopaedic Research

  9. Mechanisms involved in the transport of mercuric ions in target tissues

    Science.gov (United States)

    Bridges, Christy C.; Zalups, Rudolfs K.

    2016-01-01

    Mercury exists in the environment in various forms, all of which pose a risk to human health. Despite guidelines regulating the industrial release of mercury into the environment, humans continue to be exposed regularly to various forms of this metal via inhalation or ingestion. Following exposure, mercuric ions are taken up by and accumulate in numerous organs, including brain, intestine, kidney, liver, and placenta. In order to understand the toxicological effects of exposure to mercury, a thorough understanding of the mechanisms that facilitate entry of mercuric ions into target cells must first be obtained. A number of mechanisms for the transport of mercuric ions into target cells and organs have been proposed in recent years. However, the ability of these mechanisms to transport mercuric ions and the regulatory features of these carriers have not been characterized completely. The purpose of this review is to summarize the current findings related to the mechanisms that may be involved in the transport of inorganic and organic forms of mercury in target tissues and organs. This review will describe mechanisms known to be involved in the transport of mercury and will also propose additional mechanisms that may potentially be involved in the transport of mercuric ions into target cells. PMID:27422290

  10. Active Tension Network model reveals an exotic mechanical state realized in epithelial tissues

    Science.gov (United States)

    Noll, Nicholas; Mani, Madhav; Heemskerk, Idse; Streicha, Sebastian; Shraiman, Boris

    Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behavior remains an open problem. Here we formulate and analyze the Active Tension Network (ATN) model, which assumes that mechanical balance of cells is dominated by cortical tension and introduces tension dependent active remodeling of the cortex. We find that ATNs exhibit unusual mechanical properties: i) ATN behaves as a fluid at short times, but at long times it supports external tension, like a solid; ii) its mechanical equilibrium state has extensive degeneracy associated with a discrete conformal - ''isogonal'' - deformation of cells. ATN model predicts a constraint on equilibrium cell geometry, which we demonstrate to hold in certain epithelial tissues. We further show that isogonal modes are observed in a fruit fly embryo, accounting for the striking variability of apical area of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, understanding which helps understand biological phenomena.

  11. Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury: mechanisms of brain tissue repair

    Directory of Open Access Journals (Sweden)

    Zhen-qiang Zhang

    2016-01-01

    Full Text Available Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury, but the underlying mechanisms remain unclear. In this study, rats were intragastrically given Buyanghuanwu decoction, 15 mL/kg, for 3 days. A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion. In rats administered Buyanghuanwu decoction, infarct volume was reduced, serum vascular endothelial growth factor and integrin αvβ3 levels were increased, and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals. These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor (administered through the lateral ventricle for 7 consecutive days. These data suggest that Buyanghuanwu decoction promotes angiogenesis, improves cerebral circulation, and enhances brain tissue repair after cerebral ischemia/reperfusion injury.

  12. Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.

    Science.gov (United States)

    Gaut, Carrie; Sugaya, Kiminobu

    2015-01-01

    Articular cartilage defects often progress to osteoarthritis, which negatively impacts quality of life for millions of people worldwide and leads to high healthcare expenditures. Tissue engineering approaches to osteoarthritis have concentrated on proliferation and differentiation of stem cells by activation and suppression of signaling pathways, and by using a variety of scaffolding techniques. Recent studies indicate a key role of environmental factors in the differentiation of mesenchymal stem cells to mature cartilage-producing chondrocytes. Therapeutic approaches that consider environmental regulation could optimize chondrogenesis protocols for regeneration of articular cartilage. This review focuses on the effect of scaffold structure and composition, mechanical stress and hypoxia in modulating mesenchymal stem cell fate and the current use of these environmental factors in tissue engineering research.

  13. Identification of molecular mechanisms of radiation-induced vascular damage in normal tissues using microarray analyses

    International Nuclear Information System (INIS)

    Kruse, J.J.C.M.; Te Poele, J.A.M.; Russell, N.S.; Boersma, L.J.; Stewart, F.A.

    2003-01-01

    Radiation-induced telangiectasia, characterized by thin-walled dilated blood vessels, can be a serious late complication in patients that have been previously treated for cancer. It might cause cosmetic problems when occurring in the skin, and excessive bleeding requiring surgery when occurring in rectal mucosa. The mechanisms underlying the development of radiation-induced telangiectasia are unclear. The aim of the present study is to determine whether microarrays are useful for studying mechanisms of radiation-induced telangiectasia. The second aim is to test the hypotheses that telangiectasia is characterized by a final common pathway in different tissues. Microarray experiments were performed using amplified RNA from (sham)irradiated mouse tissues (kidney, rectum) at different intervals (1-30 weeks) after irradiation. After normalization procedures, the differentially expressed genes were identified. Control/repeat experiments were done to confirm that the observations were not artifacts of the array procedure. The mouse kidney experiments showed significant upregulation of 31 and 42 genes and downregulation of 9 and 4 genes at 10 and 20 weeks after irradiation, respectively. Irradiated mouse rectum has 278 upregulated and 537 downregulated genes at 10 weeks and 86 upregulated and 29 downregulated genes at 20 weeks. During the development of telangiectasia, 19 upregulated genes and 5 downregulated genes were common to both tissues. Upregulation of Jagged-1, known to play a role in angiogenesis, is particularly interesting in the context of radiation-induced telangiectasia. Microarrays are affective discovery tools to identify novel genes of interest, which may be involved in radiation-induced normal tissue injury. Using information from control arrays (particularly straight color, color reverse and self-self experiments) allowed for a more accurate and reproducible identification of differentially expressed genes than the selection of an arbitrary 2-fold change

  14. A novel laparoscopic grasper with two parallel jaws capable of extracting the mechanical behaviour of soft tissues.

    Science.gov (United States)

    Nazarynasab, Dariush; Farahmand, Farzam; Mirbagheri, Alireza; Afshari, Elnaz

    2017-07-01

    Data related to force-deformation behaviour of soft tissue plays an important role in medical/surgical applications such as realistically modelling mechanical behaviour of soft tissue as well as minimally invasive surgery (MIS) and medical diagnosis. While the mechanical behaviour of soft tissue is very complex due to its different constitutive components, some issues increase its complexity like behavioural changes between the live and dead tissues. Indeed, an adequate quantitative description of mechanical behaviour of soft tissues requires high quality in vivo experimental data to be obtained and analysed. This paper describes a novel laparoscopic grasper with two parallel jaws capable of obtaining compressive force-deformation data related to mechanical behaviour of soft tissues. This new laparoscopic grasper includes four sections as mechanical hardware, sensory part, electrical/electronical part and data storage part. By considering a unique design for mechanical hardware, data recording conditions will be close to unconfined-compression-test conditions; so obtained data can be properly used in extracting the mechanical behaviour of soft tissues. Also, the other distinguishing feature of this new system is its applicability during different laparoscopic surgeries and subsequently obtaining in vivo data. However, more preclinical examinations are needed to evaluate the practicality of the novel laparoscopic grasper with two parallel jaws.

  15. Analysis of heel pad tissues mechanics at the heel strike in bare and shod conditions.

    Science.gov (United States)

    Fontanella, C G; Forestiero, A; Carniel, E L; Natali, A N

    2013-04-01

    A combined experimental and numerical approach is used to investigate the interaction phenomena occurring between foot and footwear during the heel strike phase of the gait. Two force platforms are utilised to evaluate the ground reaction forces of a subject in bare and shod walking. The reaction forces obtained from the experimental tests are assumed as loading conditions for the numerical analyses using three dimensional models of the heel region and of the running shoe. The heel pad region, as fat and skin tissues, is described by visco-hyperelastic and fibre-reinforced hyperelastic formulations respectively and bone region by a linear orthotropic formulation. Different elastomeric foams are considered with regard to the outsole, the midsole and the insole layers. The mechanical properties are described by a hyperfoam formulation. The evaluation of the mechanical behaviour of the heel pad tissues at the heel strike in bare and shod conditions is performed considering different combinations of materials for midsole and insole layers. Results allow for the definition of the influence of different material characteristics on the mechanical response of the heel pad region, in particular showing the compressive stress differentiation in the bare and shod conditions. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

  16. Mechanical and mineral properties of osteogenesis imperfecta human bones at the tissue level.

    Science.gov (United States)

    Imbert, Laurianne; Aurégan, Jean-Charles; Pernelle, Kélig; Hoc, Thierry

    2014-08-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by an increase in bone fragility on the macroscopic scale, but few data are available to describe the mechanisms involved on the tissue scale and the possible correlations between these scales. To better understand the effects of OI on the properties of human bone, we studied the mechanical and chemical properties of eight bone samples from children suffering from OI and compared them to the properties of three controls. High-resolution computed tomography, nanoindentation and Raman microspectroscopy were used to assess those properties. A higher tissue mineral density was found for OI bone (1.131 gHA/cm3 vs. 1.032 gHA/cm3, p=0.032), along with a lower Young's modulus (17.6 GPa vs. 20.5 GPa, p=0.024). Obviously, the mutation-induced collagen defects alter the collagen matrix, thereby affecting the mineralization. Raman spectroscopy showed that the mineral-to-matrix ratio was higher in the OI samples, while the crystallinity was lower, suggesting that the mineral crystals were smaller but more abundant in the case of OI. This change in crystal size, distribution and composition contributes to the observed decrease in mechanical strength. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering.

    Science.gov (United States)

    Gelmi, Amy; Cieslar-Pobuda, Artur; de Muinck, Ebo; Los, Marek; Rafat, Mehrdad; Jager, Edwin W H

    2016-06-01

    The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Factors affecting the mechanical behavior of collagen hydrogels for skin tissue engineering.

    Science.gov (United States)

    Pensalfini, Marco; Ehret, Alexander E; Stüdeli, Silvia; Marino, Daniela; Kaech, Andres; Reichmann, Ernst; Mazza, Edoardo

    2017-05-01

    The effect of the production factors yielding a functional dermal substitute was investigated by means of monotonic and cyclic uniaxial tensile tests, as well as electron microscopy visualizations. The role of (i) plastic compression, (ii) product incubation, and (iii) cell permanence in the collagenous matrix in order to achieve a skin-like behavior were characterized in terms of material and structural stiffness, in-plane kinematics, and cyclic response, as well as pore size and network density. The plastic compression resulted in a denser and stiffer material, while no corresponding change was observed in the behavior of the entire structure. This was related to the progressive reduction in product thickness and amount of excess water, rather than to formation of new crosslinks between fibers. Contrary, irrespective of the presence of human fibroblasts, the product incubation induced both material and structural stiffening, indicating the formation of a denser network. These results were confirmed by similar evolutions in the construct in-plane kinematics and cyclic stress reduction. Finally, comparison of constructs incubated in different culture media indicated a determinant contribution of the biochemical environment, rather than of the seeded cells, to the achieved mechanical properties. The observed features are relevant in terms of mechanical biocompatibility of the implant and might direct future optimizations of the production process in order to rapidly attain the desired mechanical properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Chemo-mechanical modeling of tumor growth in elastic epithelial tissue

    Science.gov (United States)

    Bratsun, Dmitry A.; Zakharov, Andrey P.; Pismen, Len

    2016-08-01

    We propose a multiscale chemo-mechanical model of the cancer tumor development in the epithelial tissue. The epithelium is represented by an elastic 2D array of polygonal cells with its own gene regulation dynamics. The model allows the simulation of the evolution of multiple cells interacting via the chemical signaling or mechanically induced strain. The algorithm includes the division and intercalation of cells as well as the transformation of normal cells into a cancerous state triggered by a local failure of the spatial synchronization of the cellular rhythms driven by transcription/translation processes. Both deterministic and stochastic descriptions of the system are given for chemical signaling. The transformation of cells means the modification of their respective parameters responsible for chemo-mechanical interactions. The simulations reproduce a distinct behavior of invasive and localized carcinoma. Generally, the model is designed in such a way that it can be readily modified to take account of any newly understood gene regulation processes and feedback mechanisms affecting chemo-mechanical properties of cells.

  20. Chemo-mechanical modeling of tumor growth in elastic epithelial tissue

    Energy Technology Data Exchange (ETDEWEB)

    Bratsun, Dmitry A., E-mail: bratsun@pspu.ru [Department of Applied Physics, Perm National Research Polytechnical University, Perm, 614990 (Russian Federation); Zakharov, Andrey P. [Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa, 32000 Israel (Israel); Theoretical Physics Department, Perm State Humanitarian Pedagogical University, Perm, 614990 (Russian Federation); Pismen, Len [Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa, 32000 Israel (Israel)

    2016-08-02

    We propose a multiscale chemo-mechanical model of the cancer tumor development in the epithelial tissue. The epithelium is represented by an elastic 2D array of polygonal cells with its own gene regulation dynamics. The model allows the simulation of the evolution of multiple cells interacting via the chemical signaling or mechanically induced strain. The algorithm includes the division and intercalation of cells as well as the transformation of normal cells into a cancerous state triggered by a local failure of the spatial synchronization of the cellular rhythms driven by transcription/translation processes. Both deterministic and stochastic descriptions of the system are given for chemical signaling. The transformation of cells means the modification of their respective parameters responsible for chemo-mechanical interactions. The simulations reproduce a distinct behavior of invasive and localized carcinoma. Generally, the model is designed in such a way that it can be readily modified to take account of any newly understood gene regulation processes and feedback mechanisms affecting chemo-mechanical properties of cells.

  1. Three-dimensional fiber-deposited PEOT/PBT copolymer scaffolds for tissue engineering: influence of porosity molecular network mesh size, and swelling in aqueous media on dynamic mechanical properties

    NARCIS (Netherlands)

    Moroni, Lorenzo; de Wijn, J.R.; van Blitterswijk, Clemens

    2005-01-01

    Among novel scaffold fabrication techniques, 3D fiber deposition (3DF) has recently emerged as a means to fabricate well-defined and custom-made scaffolds for tissue regeneration, with 100% interconnected pores. The mechanical behavior of these constructs is dependent not only on different

  2. Possible role of mechanical force in regulating regeneration of the vascularized fat flap inside a tissue engineering chamber.

    Science.gov (United States)

    Ye, Yuan; Yuan, Yi; Lu, Feng; Gao, Jianhua

    2015-12-01

    In plastic and reconstructive surgery, adipose tissue is widely used as effective filler for tissue defects. Strategies for treating soft tissue deficiency, which include free adipose tissue grafts, use of hyaluronic acid, collagen injections, and implantation of synthetic materials, have several clinical limitations. With the aim of overcoming these limitations, researchers have recently utilized tissue engineering chambers to produce large volumes of engineered vascularized fat tissue. However, the process of growing fat tissue in a chamber is still relatively limited, and can result in unpredictable or dissatisfactory final tissue volumes. Therefore, detailed understanding of the process is both necessary and urgent. Many studies have shown that mechanical force can change the function of cells via mechanotransduction. Here, we hypothesized that, besides the inflammatory response, one of the key factors to control the regeneration of vascularized fat flap inside a tissue engineering chamber might be the balance of mechanical forces. To test our hypothesis, we intend to change the balance of forces by means of measures in order to make the equilibrium point in favor of the direction of regeneration. If those measures proved to be feasible, they could be applied in clinical practice to engineer vascularized adipose tissue of predictable size and shape, which would in turn help in the advancement of tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Multi-scale modeling of soft fibrous tissues based on proteoglycan mechanics.

    Science.gov (United States)

    Linka, Kevin; Khiêm, Vu Ngoc; Itskov, Mikhail

    2016-08-16

    Collagen in the form of fibers or fibrils is an essential source of strength and structural integrity in most organs of the human body. Recently, with the help of complex experimental setups, a paradigm change concerning the mechanical contribution of proteoglycans (PGs) took place. Accordingly, PG connections protect the surrounding collagen fibrils from over-stretching rather than transmitting load between them. In this paper, we describe the reported PG mechanics and incorporate it into a multi-scale model of soft fibrous tissues. To this end, a nano-to-micro model of a single collagen fiber is developed by taking the entropic-energetic transition on the collagen molecule level into account. The microscopic damage occurring inside the collagen fiber is elucidated by sliding of PGs as well as by over-stretched collagen molecules. Predictions of this two-constituent-damage model are compared to experimental data available in the literature. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. On the characterization of the heterogeneous mechanical response of human brain tissue.

    Science.gov (United States)

    Forte, Antonio E; Gentleman, Stephen M; Dini, Daniele

    2017-06-01

    The mechanical characterization of brain tissue is a complex task that scientists have tried to accomplish for over 50 years. The results in the literature often differ by orders of magnitude because of the lack of a standard testing protocol. Different testing conditions (including humidity, temperature, strain rate), the methodology adopted, and the variety of the species analysed are all potential sources of discrepancies in the measurements. In this work, we present a rigorous experimental investigation on the mechanical properties of human brain, covering both grey and white matter. The influence of testing conditions is also shown and thoroughly discussed. The material characterization performed is finally adopted to provide inputs to a mathematical formulation suitable for numerical simulations of brain deformation during surgical procedures.

  5. Evaluation Research as a Mechanism for Critical Inquiry and Knowledge Construction in Architectural and Urban Education

    Directory of Open Access Journals (Sweden)

    Ashraf M. Salama

    2012-12-01

    Full Text Available This article responds to the misconceptions that continue to characterize the delivery of knowledge content in architectural courses. Based on reviewing the literature on pedagogy the paper explores the value and benefits of introducing evaluation research as a mechanism for critical inquiry and knowledge construction in theory courses in architecture and urbanism. A framework is developed and employed to demonstrate the way in which this type of learning can be incorporated.   The development and implementation of a series of in-class and off campus exercises in two different contexts reveal that structured actions and experiences help students to be in control over their learning while invigorating their understanding of the body of knowledge delivered in a typical lecture format. It firmly believed that this would offer students multiple learning opportunities while fostering their capabilities to shift from passive listeners to active learners and from knowledge consumers to knowledge producers.

  6. Influence of heat treatment on mechanical property of steel hollow sphere and its sheet construction

    Science.gov (United States)

    Yoshida, Yoshinori; Ozawa, Sho

    2017-10-01

    Heat treatments, water quenching and annealing, are performed on the metallic hollow spheres (MHS) made from steel with 4.0 mm in outer diameter. They are pierced then put on a piece of tungsten alloy wire for making a MHS thread. The thread is set in between two neighboring warps of the tungsten alloy and the thread is placed in a reticular pattern. The MHS fabric sheet which has plain weave structure is produced by the weaving process. Furthermore, a sandwich construction of the sheet with 2 sheets of aluminum plate. The influence of the heat treatments on difference of mechanical and energy absorption property are evaluated by mean of compression test for the sheet along with the thickness direction. In addition, an aluminum pipe is filled with a heat treated MHS sheet and compression test is performed for the pipe along the radial direction. Its difference of compression load and energy consumption property is investigated.

  7. Extending Mechanical Construction Kits to Incorporate Passive and Compliant Elements for Educational Robotics

    DEFF Research Database (Denmark)

    Assaf, Dorit; Larsen, Jørgen Christian; Reichardt, Markus

    2012-01-01

    artificial intelligence and biomechanics to students with different backgrounds. The robots we use both for research and education are usually built incorporating compliant materials as well as passive dynamics. These kind of properties are often not available in classical robot kits or mechanical......Robots are a popular educational tool to introduce science, technology, and engineering to students. The field of educational robotics is growing and consequently a number of ducational robot kits have been developed within the last decade. Our laboratories have radition of teaching embodied...... construction kits. In this paper we describe some of the robots we use for education. So far we built the robots using 3D printing technology which is convenient but too expensive for class use. Our aim is to find cheaper, commercially available solutions. After a short review on educational robot kits...

  8. Research into mechanical properties and structure of metals as part of restored construction facilities

    Directory of Open Access Journals (Sweden)

    Gustov Yuriy Ivanovich

    2014-12-01

    Full Text Available The article represents a summarized methodology of the research into small-size pilot metal samples of restored construction facilities. In the article, the co-authors demonstrate an option that provides for the analytical identification of standard characteristic values of mechanical properties, based on initial hardness HRB and conversion of hardness values using the Brinell test. Towards this end, analytical dependence of HB hardness on HRB and HRC is proposed. The numerical identification of the temporary resistance to tensile stress σ в required the pre-setting of the value of the average coefficient of relative elongation. This average coefficient was employed to identify the values of relative elongation and contraction, as well as the yield value of the metal. Standard plasticity and strength values were employed to compile an equation for complex criterion C. This criterion was employed to identify the value of relative uniform elongation and transverse contraction, and both were employed to assess the resistance to tensile stress and fatigue. The optical microscopy method was used to identify the pilot sample of the metal as structural carbon steel having grade C15. Its strength analysis based on the properties of its structural components has proven the identity between the sample metal and the aforementioned steel grade. The method proposed by the co-authors helps to identify the metals of restructured construction facilities on the basis of small-size samples to avoid the collapse of metal structures.

  9. A comparative study of tissue-engineered constructs from Acropora and Porites coral in a large animal bone defect model

    Science.gov (United States)

    Manassero, M.; Bensidhoum, M.; Lecuelle, B.; Logeart-Avramoglou, D.; Petite, H.; Viateau, V.

    2017-01-01

    Objectives To compare the therapeutic potential of tissue-engineered constructs (TECs) combining mesenchymal stem cells (MSCs) and coral granules from either Acropora or Porites to repair large bone defects. Materials and Methods Bone marrow-derived, autologous MSCs were seeded on Acropora or Porites coral granules in a perfusion bioreactor. Acropora-TECs (n = 7), Porites-TECs (n = 6) and bone autografts (n = 2) were then implanted into 25 mm long metatarsal diaphyseal defects in sheep. Bimonthly radiographic follow-up was completed until killing four months post-operatively. Explants were subsequently processed for microCT and histology to assess bone formation and coral bioresorption. Statistical analyses comprised Mann-Whitney, t-test and Kruskal–Wallis tests. Data were expressed as mean and standard deviation. Results A two-fold increaseof newly formed bone volume was observed for Acropora-TECs when compared with Porites-TECs (14 sd 1089 mm3 versus 782 sd 507 mm3; p = 0.09). Bone union was consistent with autograft (1960 sd 518 mm3). The kinetics of bioresorption and bioresorption rates at four months were different for Acropora-TECs and Porites-TECs (81% sd 5% versus 94% sd 6%; p = 0.04). In comparing the defects that healed with those that did not, we observed that, when major bioresorption of coral at two months occurs and a scaffold material bioresorption rate superior to 90% at four months is achieved, bone nonunion consistently occurred using coral-based TECs. Discussion Bone regeneration in critical-size defects could be obtained with full bioresorption of the scaffold using coral-based TECs in a large animal model. The superior performance of Acropora-TECs brings us closer to a clinical application, probably because of more suitable bioresorption kinetics. However, nonunion still occurred in nearly half of the bone defects. Cite this article: A. Decambron, M. Manassero, M. Bensidhoum, B. Lecuelle, D. Logeart-Avramoglou, H. Petite, V. Viateau. A

  10. Computational Simulation of the Mechanical Response of Brain Tissue under Blast Loading

    Science.gov (United States)

    Laksari, Kaveh; Assari, Soroush; Seibold, Benjamin; Sadeghipour, Keya; Darvish, Kurosh

    2014-01-01

    In the present study, numerical simulations of nonlinear wave propagation and shock formation in brain tissue have been presented and a new mechanism of injury for Blast-Induced Neurotrauma (BINT) is proposed. A quasilinear viscoelastic (QLV) constitutive material model was used that encompasses the nonlinearity as well as the rate dependence of the tissue relevant to BINT modeling. A one-dimensional model was implemented using the discontinuous Galerkin -finite element method and studied with displacement-input and pressure-input boundary conditions. The model was validated against LS-DYNA finite element code and theoretical results for speci c conditions that resulted in shock wave formation. It was shown that a continuous wave can become a shock wave as it propagates in the QLV brain tissue when the initial changes in acceleration are beyond a certain limit. The high spatial gradient of stress and strain at the shock front cause large relative motions at the cellular scale at high temporal rates even when the maximum stresses and strains are relatively low. This gradient-induced local deformation may occur away from the boundary and is proposed as a contributing factor to the diffuse nature of BINT. PMID:25205088

  11. Combining mechanical foaming and thermally induced phase separation to generate chitosan scaffolds for soft tissue engineering.

    Science.gov (United States)

    Biswas, D P; Tran, P A; Tallon, C; O'Connor, A J

    2017-02-01

    In this paper, a novel foaming methodology consisting of turbulent mixing and thermally induced phase separation (TIPS) was used to generate scaffolds for tissue engineering. Air bubbles were mechanically introduced into a chitosan solution which forms the continuous polymer/liquid phase in the foam created. The air bubbles entrained in the foam act as a template for the macroporous architecture of the final scaffolds. Wet foams were crosslinked via glutaraldehyde and frozen at -20 °C to induce TIPS in order to limit film drainage, bubble coalescence and Ostwald ripening. The effects of production parameters, including mixing speed, surfactant concentration and chitosan concentration, on foaming are explored. Using this method, hydrogel scaffolds were successfully produced with up to 80% porosity, average pore sizes of 120 μm and readily tuneable compressive modulus in the range of 2.6 to 25 kPa relevant to soft tissue engineering applications. These scaffolds supported 3T3 fibroblast cell proliferation and penetration and therefore show significant potential for application in soft tissue engineering.

  12. Protein Redox Modification as a Cellular Defense Mechanism against Tissue Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Liang-Jun Yan

    2014-01-01

    Full Text Available Protein oxidative or redox modifications induced by reactive oxygen species (ROS or reactive nitrogen species (RNS not only can impair protein function, but also can regulate and expand protein function under a variety of stressful conditions. Protein oxidative modifications can generally be classified into two categories: irreversible oxidation and reversible oxidation. While irreversible oxidation usually leads to protein aggregation and degradation, reversible oxidation that usually occurs on protein cysteine residues can often serve as an “on and off” switch that regulates protein function and redox signaling pathways upon stress challenges. In the context of ischemic tolerance, including preconditioning and postconditioning, increasing evidence has indicated that reversible cysteine redox modifications such as S-sulfonation, S-nitrosylation, S-glutathionylation, and disulfide bond formation can serve as a cellular defense mechanism against tissue ischemic injury. In this review, I highlight evidence of cysteine redox modifications as protective measures in ischemic injury, demonstrating that protein redox modifications can serve as a therapeutic target for attenuating tissue ischemic injury. Prospectively, more oxidatively modified proteins will need to be identified that can play protective roles in tissue ischemic injury, in particular, when the oxidative modifications of such identified proteins can be enhanced by pharmacological agents or drugs that are available or to be developed.

  13. Comparative Research on Human Settlements in Asian Rural Areas Based on Collaborative Construction Mechanism

    Science.gov (United States)

    Xin, Sui; Chaoyang, Sun; Mo, Li

    2018-02-01

    Rural planning is perceived as a spatial planning centered on the human settlements and there are many activities for rural reconstruction and researches conducted from the perspective of active intervention, with fewer studies regarding the village as the main body for the establishment of self-built system. And the other-organization built by the rural areas is strongly oriented. In Asian countries like China, South Korea and Japan, there are farming traditions, in which the familial and small-scale farmland holding and agricultural production mode are deep-rooted. Traditional agriculture and rural areas are not fundamentally changed by industrialization and modernization process. And the small-scale peasant in the East is marked by the decentralized possession of farmland and management in the rural areas and a large number of farmers to be remained. But the rural population keeps decreasing. After analyzing the status quo of human settlements in China, Korea and Japan, the paper makes an analysis from the different ways of thinking and professional perspective and focuses on putting forward the solutions to the problems on macro level, with the feasibility of the practical significance and the landing researches still staying in the testing stage. In the context of increasingly missing regional and contextual features, the launching and researches of “co-constructed community” as the folk protection way to emerging rural heritage are just started, and the researches on rural construction in Northeast China from the perspective of catalyst are absent. The contact agent with the catalytic action mechanism of seeing big things through small ones fits the rural areas marked by vast territory and diversified aspect, which is applicable to the bottom-up operation mechanism autonomously built by the villagers.

  14. Improved contractile force generation of tissue-engineered skeletal muscle constructs by IGF-I and Bcl-2 gene transfer with electrical pulse stimulation

    OpenAIRE

    Ikeda, Kazushi; Ito, Akira; Sato, Masanori; Kawabe, Yoshinori; Kamihira, Masamichi

    2016-01-01

    Introduction: Tissue-engineered skeletal muscle constructs should be designed to generate contractile force with directional movement. Because electrical impulses from a somatic nervous system are crucial for in vivo skeletal muscle development, electrical pulse stimulation (EPS) culture as an artificial exercise is essential to fabricate functional skeletal muscle tissues in vitro. To further improve muscle functions, the activation of cell-signaling pathways from myogenic growth factors, su...

  15. Static and dynamic mechanics of the TMJ: Plowing forces, joint load, and tissue stress

    Science.gov (United States)

    Nickel, J; Spilker, R; Iwasaki, L; Gonzalez, Y; McCall, WD; Ohrbach, R; Beatty, MW; Marx, D

    2009-01-01

    Objectives To determine (1) the combined effects of stress-field aspect ratio and velocity, and compressive strain, and (2) joint load, on TMJ disc mechanics Setting and Sample Population Fifty-two subjects (30 ♀; 20 ♂ ) participated in the TMJ load experiments. Material and Methods In the absence of human tissue, pig TMJ discs were used to determine the effects of variables (1) on surface plowing forces, and to build a biphasic finite element model (bFEM) to test the effect of human joint loads (2) on tissue stresses. In the laboratory, discs received a 7.6 N static load via an acrylic indenter before cyclic movement. Data were recorded and analyzed using ANOVA. To determine human joint loads (2), Research Diagnostic Criteria (RDC) calibrated investigators classified subjects based on signs of disc displacement (DD) and pain (+DD/+Pain, n=18; +DD/-Pain, n=17; -DD/-Pain, n=17). 3-D geometries were produced for each subject and used in a computer model to calculate joint loads. Results The combined effects of compressive strain, and aspect ratio and velocity of stress-field translation correlated with plowing forces (R2=0.85). +DD/-Pain subjects produced 60% higher joint loads (ANOVA, PStatic and dynamic variables of the stress-field and subject dependent joint load significantly affect disc mechanics. PMID:19627517

  16. Static and dynamic mechanics of the temporomandibular joint: plowing forces, joint load and tissue stress.

    Science.gov (United States)

    Nickel, J; Spilker, R; Iwasaki, L; Gonzalez, Y; McCall, W D; Ohrbach, R; Beatty, M W; Marx, D

    2009-08-01

    OBJECTIVES - To determine the combined effects 1) of stress-field aspect ratio and velocity and compressive strain and 2) joint load, on temporomandibular joint (TMJ) disc mechanics. SETTING AND SAMPLE POPULATION - Fifty-two subjects (30 female; 22 male) participated in the TMJ load experiments. MATERIAL AND METHODS - In the absence of human tissue, pig TMJ discs were used to determine the effects of variables 1) on surface plowing forces, and to build a biphasic finite element model (bFEM) to test the effect of human joint loads and 2) on tissue stresses. In the laboratory, discs received a 7.6 N static load via an acrylic indenter before cyclic movement. Data were recorded and analysed using anova. To determine human joint loads, Research Diagnostic Criteria calibrated investigators classified subjects based on signs of disc displacement (DD) and pain (+DD/+pain, n = 18; +DD/-pain, n = 17; -DD/-pain, n = 17). Three-dimensional geometries were produced for each subject and used in a computer model to calculate joint loads. RESULTS - The combined effects of compressive strain, and aspect ratio and velocity of stress-field translation correlated with plowing forces (R(2) = 0.85). +DD/-pain subjects produced 60% higher joint loads (ANOVA, p Static and dynamic variables of the stress-field and subject-dependent joint load significantly affect disc mechanics.

  17. Contribution of elastic tissues to the mechanics and energetics of muscle function during movement.

    Science.gov (United States)

    Roberts, Thomas J

    2016-01-01

    Muscle force production occurs within an environment of tissues that exhibit spring-like behavior, and this elasticity is a critical determinant of muscle performance during locomotion. Muscle force and power output both depend on the speed of contraction, as described by the isotonic force-velocity curve. By influencing the speed of contractile elements, elastic structures can have a profound effect on muscle force, power and work. In very rapid movements, elastic mechanisms can amplify muscle power by storing the work of muscle contraction slowly and releasing it rapidly. When energy must be dissipated rapidly, such as in landing from a jump, energy stored rapidly in elastic elements can be released more slowly to stretch muscle contractile elements, reducing the power input to muscle and possibly protecting it from damage. Elastic mechanisms identified so far rely primarily on in-series tendons, but many structures within muscles exhibit spring-like properties. Actomyosin cross-bridges, actin and myosin filaments, titin, and the connective tissue scaffolding of the extracellular matrix all have the potential to store and recover elastic energy during muscle contraction. The potential contribution of these elements can be assessed from their stiffness and estimates of the strain they undergo during muscle function. Such calculations provide boundaries for the possible roles these springs might play in locomotion, and may help to direct future studies of the uses of elastic elements in muscle. © 2016. Published by The Company of Biologists Ltd.

  18. Mechanical analysis of bone rulers sterilized by gamma radiation for use in tissue banks

    International Nuclear Information System (INIS)

    Kosmiskas, Luis Otavio Carvalho

    2007-01-01

    In the production process of health care products, contamination must be considered as one of the principal hazards to be avoided. Among the developed methods for sterilization, ionizing radiation has largely been used by many sectors in health care area as it is efficient in eliminating biological contaminants of several origins. The difficulty of deploying ionizing radiation in materials of human origin, though, includes which possible alterations it might cause in human tissue. In the present work, the extension of the bio mechanical alteration generated by radiation in bone tissue was evaluated by bio mechanical methods. More specifically, we evaluated alterations to the elastic modulus, rupture tension and percentage of deformation that are thought to be a consequence of the sterilization process. As a research model, bovine femur struts obtained from the diaphysis were used. The struts were frozen in a temperature of -70 deg C and irradiated with crescent doses of gamma radiation (0, 12.5, 25 e 50 kGy). During this work, a cutting system to obtain precision samples to use in such essays was developed. As results show that there is a significant different between the analyzed characteristics in the different doses of radiation. (author)

  19. Fabrication and mechanical characterization of a polyvinyl alcohol sponge for tissue engineering applications.

    Science.gov (United States)

    Karimi, A; Navidbakhsh, M; Faghihi, S

    2014-05-01

    Polyvinyl alcohol (PVA) sponges are widely used for clinical applications, including ophthalmic surgical treatments, wound healing and tissue engineering. There is, however, a lack of sufficient data on the mechanical properties of PVA sponges. In this study, a biomechanical method is used to characterize the elastic modulus, maximum stress and strain as well as the swelling ratio of a fabricated PVA sponge (P-sponge) and it is compared with two commercially available PVA sponges (CENEFOM and EYETEC). The results indicate that the elastic modulus of the P-sponge is 5.32% and 13.45% lower than that of the CENEFOM and EYETEC sponges, while it bears 4.11% more and 10.37% less stress compared to the CENEFOM and EYETEC sponges, respectively. The P-sponge shows a maximum strain of 32% more than the EYETEC sponge as well as a 26.78% higher swelling ratio, which is a significantly higher absorbency compared to the CENEFOM. It is believed that the results of this study would help for a better understanding of the extension, rupture and swelling mechanism of PVA sponges, which could lead to crucial improvement in the design and application of PVA-based materials in ophthalmic and plastic surgeries as well as wound healing and tissue engineering.

  20. Improving the mechanical properties of collagen-based membranes using silk fibroin for corneal tissue engineering.

    Science.gov (United States)

    Long, Kai; Liu, Yang; Li, Weichang; Wang, Lin; Liu, Sa; Wang, Yingjun; Wang, Zhichong; Ren, Li

    2015-03-01

    Although collagen with outstanding biocompatibility has promising application in corneal tissue engineering, the mechanical properties of collagen-based scaffolds, especially suture retention strength, must be further improved to satisfy the requirements of clinical applications. This article describes a toughness reinforced collagen-based membrane using silk fibroin. The collagen-silk fibroin membranes based on collagen [silk fibroin (w/w) ratios of 100:5, 100:10, and 100:20] were prepared by using silk fibroin and cross-linking by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. These membranes were analyzed by scanning electron microscopy and their optical property, and NaCl and tryptophan diffusivity had been tested. The water content was found to be dependent on the content of silk fibroin, and CS10 membrane (loading 10 wt % of silk fibroin) performed the optimal mechanical properties. Also the suture experiments have proved CS10 has high suture retention strength, which can be sutured in rabbit eyes integrally. Moreover, the composite membrane proved good biocompatibility for the proliferation of human corneal epithelial cells in vitro. Lamellar keratoplasty shows that CS10 membrane promoted complete epithelialization in 35 ± 5 days, and their transparency is restored quickly in the first month. Corneal rejection reaction, neovascularization, and keratoconus are not observed. The composite films show potential for use in the field of corneal tissue engineering. © 2014 Wiley Periodicals, Inc.

  1. Mechanism of the tissue-specific action of the selective androgen receptor modulator S-101479.

    Science.gov (United States)

    Furuya, Kazuyuki; Yamamoto, Noriko; Ohyabu, Yuki; Morikyu, Teruyuki; Ishige, Hirohide; Albers, Michael; Endo, Yasuhisa

    2013-01-01

    Selective androgen receptor modulators (SARMs) comprise a new class of molecules that induce anabolic effects with fewer side effects than those of other anabolic agents. We previously reported that the novel SARM S-101479 had a tissue-selective bone anabolic effect with diminished side effects in female animals. However, the mechanism of its tissue selectivity is not well known. In this report, we show that S-101479 increased alkaline phosphatase activity and androgen receptor (AR) transcriptional activity in osteoblastic cell lines in the same manner as the natural androgen ligand dihydrotestosterone (DHT); conversely, stimulation of AR dimerization was very low compared with that of DHT (34.4%). S-101479 increased bone mineral content in ovariectomized rats without promoting endometrial proliferation. Yeast two-hybrid interaction assays revealed that DHT promoted recruitment of numerous cofactors to AR such as TIF2, SRC1, β-catenin, NCoA3, gelsolin and PROX1 in a dose-dependent manner. SARMs induced recruitment of fewer cofactors than DHT; in particular, S-101479 failed to induce recruitment of canonical p160 coactivators such as SRC1, TIF2 and notably NCoA3 but only stimulated binding of AR to gelsolin and PROX1. The results suggest that a full capability of the AR to dimerize and to effectively and unselectively recruit all canonical cofactors is not a prerequisite for transcriptional activity in osteoblastic cells and resulting anabolic effects in bone tissues. Instead, few relevant cofactors might be sufficient to promote AR activity in these tissues.

  2. Advanced modeling strategy for the analysis of heart valve leaflet tissue mechanics using high-order finite element method.

    Science.gov (United States)

    Mohammadi, Hadi; Bahramian, Fereshteh; Wan, Wankei

    2009-11-01

    Modeling soft tissue using the finite element method is one of the most challenging areas in the field of biomechanical engineering. To date, many models have been developed to describe heart valve leaflet tissue mechanics, which are accurate to some extent. Nevertheless, there is no comprehensive method to modeling soft tissue mechanics, This is because (1) the degree of anisotropy in the heart valve leaflet changes layer by layer due to a variety of collagen fiber densities and orientations that cannot be taken into account in the model and also (2) a constitutive material model fully describing the mechanical properties of the leaflet structure is not available in the literature. In this framework, we develop a new high-order element using p-type finite element formulation to create anisotropic material properties similar to those of the heart valve leaflet tissue in only one single element. This element also takes the nonlinearity of the leaflet tissue into consideration using a bilinear material model. This new element is composed a two-dimensional finite element in the principal directions of leaflet tissue and a p-type finite element in the direction of thickness. The proposed element is easy to implement, much more efficient than standard elements available in commercial finite element packages. This study is one step towards the modeling of soft tissue mechanics using a meshless finite element approach to be applied in real-time haptic feedback of soft-tissue models in virtual reality simulation.

  3. Poly (Ethylene Glycol)-Based Hydrogels as Self-Inflating Tissue Expanders with Tunable Mechanical and Swelling Properties.

    Science.gov (United States)

    Jamadi, Mahsa; Shokrollahi, Parvin; Houshmand, Behzad; Joupari, Mortaza Daliri; Mashhadiabbas, Fatemeh; Khademhosseini, Ali; Annabi, Nasim

    2017-08-01

    Tissue expansion is used by plastic/reconstructive surgeons to grow additional skin/tissue for replacing or repairing lost or damaged soft tissues. Recently, hydrogels have been widely used for tissue expansion applications. Herein, a self-inflating tissue expander blend composition from three different molecular weights (2, 6, and 10 kDa) of poly (ethylene glycol) diacrylate (PEGDA) hydrogel with tunable mechanical and swelling properties is presented. The in vitro results demonstrate that, of the eight studied compositions, P6 (PEGDA 6 kDa:10 kDa (50:50)) and P8 (PEGDA 6 kDa:10 kDa (35:65)) formulations provide a balance of mechanical property and swelling capability suitable for tissue expansion. Furthermore, these expanders can be compressed up to 60% of their original height and can be loaded and unloaded cyclically at least ten times with no permanent deformation. The in vivo results indicate that these two engineered blend compositions are capable to generate a swelling pressure sufficient to dilate the surrounding tissue while retaining their original shape. The histological analyses reveal the formation of fibrous capsule at the interface between the implant and the subcutaneous tissue with no signs of inflammation. Ultimately, controlling the PEGDA chain length shows potential for the development of self-inflating tissue expanders with tunable mechanical and swelling properties. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Mechanisms of vascular damage by hemorrhagic snake venom metalloproteinases: tissue distribution and in situ hydrolysis.

    Directory of Open Access Journals (Sweden)

    Cristiani Baldo

    Full Text Available BACKGROUND: Envenoming by viper snakes constitutes an important public health problem in Brazil and other developing countries. Local hemorrhage is an important symptom of these accidents and is correlated with the action of snake venom metalloproteinases (SVMPs. The degradation of vascular basement membrane has been proposed as a key event for the capillary vessel disruption. However, SVMPs that present similar catalytic activity towards extracellular matrix proteins differ in their hemorrhagic activity, suggesting that other mechanisms might be contributing to the accumulation of SVMPs at the snakebite area allowing capillary disruption. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we compared the tissue distribution and degradation of extracellular matrix proteins induced by jararhagin (highly hemorrhagic SVMP and BnP1 (weakly hemorrhagic SVMP using the mouse skin as experimental model. Jararhagin induced strong hemorrhage accompanied by hydrolysis of collagen fibers in the hypodermis and a marked degradation of type IV collagen at the vascular basement membrane. In contrast, BnP1 induced only a mild hemorrhage and did not disrupt collagen fibers or type IV collagen. Injection of Alexa488-labeled jararhagin revealed fluorescent staining around capillary vessels and co-localization with basement membrane type IV collagen. The same distribution pattern was detected with jararhagin-C (disintegrin-like/cysteine-rich domains of jararhagin. In opposition, BnP1 did not accumulate in the tissues. CONCLUSIONS/SIGNIFICANCE: These results show a particular tissue distribution of hemorrhagic toxins accumulating at the basement membrane. This probably occurs through binding to collagens, which are drastically hydrolyzed at the sites of hemorrhagic lesions. Toxin accumulation near blood vessels explains enhanced catalysis of basement membrane components, resulting in the strong hemorrhagic activity of SVMPs. This is a novel mechanism that underlies the

  5. The effect of tissue-engineered cartilage biomechanical and biochemical properties on its post-implantation mechanical behavior

    NARCIS (Netherlands)

    Khoshgoftar, M.; Wilson, W.; Ito, K.; Donkelaar, C.C. van

    2013-01-01

    The insufficient load-bearing capacity of today's tissue-engineered (TE) cartilage limits its clinical application. Focus has been on engineering cartilage with enhanced mechanical stiffness by reproducing native biochemical compositions. More recently, depth dependency of the biochemical content

  6. Mechanical properties of gray and white matter brain tissue by indentation.

    Science.gov (United States)

    Budday, Silvia; Nay, Richard; de Rooij, Rijk; Steinmann, Paul; Wyrobek, Thomas; Ovaert, Timothy C; Kuhl, Ellen

    2015-06-01

    The mammalian brain is composed of an outer layer of gray matter, consisting of cell bodies, dendrites, and unmyelinated axons, and an inner core of white matter, consisting primarily of myelinated axons. Recent evidence suggests that microstructural differences between gray and white matter play an important role during neurodevelopment. While brain tissue as a whole is rheologically well characterized, the individual features of gray and white matter remain poorly understood. Here we quantify the mechanical properties of gray and white matter using a robust, reliable, and repeatable method, flat-punch indentation. To systematically characterize gray and white matter moduli for varying indenter diameters, loading rates, holding times, post-mortem times, and locations we performed a series of n=192 indentation tests. We found that indenting thick, intact coronal slices eliminates the common challenges associated with small specimens: it naturally minimizes boundary effects, dehydration, swelling, and structural degradation. When kept intact and hydrated, brain slices maintained their mechanical characteristics with standard deviations as low as 5% throughout the entire testing period of five days post mortem. White matter, with an average modulus of 1.89 5kPa ± 0.592 kPa, was on average 39% stiffer than gray matter, pmatter and responded less rapidly to mechanical loading. Understanding the rheological differences between gray and white matter may have direct implications on diagnosing and understanding the mechanical environment in neurodevelopment and neurological disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

    International Nuclear Information System (INIS)

    Fraenzel, W.; Gerlach, R.; Hein, H.J.; Schaller, H.G.

    2006-01-01

    Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 registered or elmex gelee registered . The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In non-irradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 registered or elmex gelee registered led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected, by remineralization than the dentine. (orig.)

  8. Mechanical loading regulates human MSC differentiation in a multi-layer hydrogel for osteochondral tissue engineering.

    Science.gov (United States)

    Steinmetz, Neven J; Aisenbrey, Elizabeth A; Westbrook, Kristofer K; Qi, H Jerry; Bryant, Stephanie J

    2015-07-01

    A bioinspired multi-layer hydrogel was developed for the encapsulation of human mesenchymal stem cells (hMSCs) as a platform for osteochondral tissue engineering. The spatial presentation of biochemical cues, via incorporation of extracellular matrix analogs, and mechanical cues, via both hydrogel crosslink density and externally applied mechanical loads, were characterized in each layer. A simple sequential photopolymerization method was employed to form stable poly(ethylene glycol)-based hydrogels with a soft cartilage-like layer of chondroitin sulfate and low RGD concentrations, a stiff bone-like layer with high RGD concentrations, and an intermediate interfacial layer. Under a compressive load, the variation in hydrogel stiffness within each layer produced high strains in the soft cartilage-like layer, low strains in the stiff bone-like layer, and moderate strains in the interfacial layer. When hMSC-laden hydrogels were cultured statically in osteochondral differentiation media, the local biochemical and matrix stiffness cues were not sufficient to spatially guide hMSC differentiation after 21 days. However dynamic mechanical stimulation led to differentially high expression of collagens with collagen II in the cartilage-like layer, collagen X in the interfacial layer and collagen I in the bone-like layer and mineral deposits localized to the bone layer. Overall, these findings point to external mechanical stimulation as a potent regulator of hMSC differentiation toward osteochondral cellular phenotypes. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. Viscoelastic behaviour of hydrogel-based composites for tissue engineering under mechanical load.

    Science.gov (United States)

    Kocen, Rok; Gasik, Michael; Gantar, Ana; Novak, Saša

    2017-03-06

    Along with biocompatibility, bioinductivity and appropriate biodegradation, mechanical properties are also of crucial importance for tissue engineering scaffolds. Hydrogels, such as gellan gum (GG), are usually soft materials, which may benefit from the incorporation of inorganic particles, e.g. bioactive glass, not only due to the acquired bioactivity, but also due to improved mechanical properties. They exhibit complex viscoelastic properties, which can be evaluated in various ways. In this work, to reliably evaluate the effect of the bioactive glass (BAG) addition on viscoelastic properties of the composite hydrogel, we employed and compared the three most commonly used techniques, analyzing their advantages and limitations: monotonic uniaxial unconfined compression, small amplitude oscillatory shear (SAOS) rheology and dynamic mechanical analysis (DMA). Creep and small amplitude dynamic strain-controlled tests in DMA are suggested as the best ways for the characterization of mechanical properties of hydrogel composites, whereas the SAOS rheology is more useful for studying the hydrogel's processing kinetics, as it does not induce volumetric changes even at very high strains. Overall, the results confirmed a beneficial effect of BAG (nano)particles on the elastic modulus of the GG-BAG composite hydrogel. The Young's modulus of 6.6 ± 0.8 kPa for the GG hydrogel increased by two orders of magnitude after the addition of 2 wt.% BAG particles (500-800 kPa).

  10. Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

    Energy Technology Data Exchange (ETDEWEB)

    Fraenzel, W. [Dept. of Physics, Martin Luther Univ. Halle (Germany); Gerlach, R. [Univ. Clinic and Policlinic for Radiation Therapy, Martin Luther Univ. Halle (Germany); Hein, H.J. [Univ. Clinic and Policlinic for Orthopaedics and Physical Medicine, Martin Luther Univ. Halle (Germany); Schaller, H.G. [Dept. of Operative Dentistry and Periodontology, Martin Luther Univ. Halle (Germany)

    2006-07-01

    Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 {sup registered} or elmex gelee {sup registered}. The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In non-irradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 {sup registered} or elmex gelee {sup registered} led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected, by remineralization than the dentine. (orig.)

  11. Quadratic Jordan formulation of quantum mechanics and construction of Lie (super)algebras from Jordan (super)algebras

    International Nuclear Information System (INIS)

    Guenaydin, M.

    1979-05-01

    Quadratic Jordan formulation of quantum mechanics in terms of Jordan triple product is presented. This formulation extends to the case of octonionic quantum mechanics for which no Hilbert space formulation exists. Using ternary algebraic techniques we then five the constructions of the derivation, structure and Tits-Koecher (Moebius) algebras of Jordan superalgebras. (orig.) [de

  12. SELECTION OF METHOD FOR REGULATION OF TRACTOR PROPULSION ASYNCHRONOUS ELECTRIC MOTOR AND CONSTRUCTION OF MECHANICAL CHARACTERISTICS

    Directory of Open Access Journals (Sweden)

    Ch. I. Zhdanovich

    2015-01-01

    laws of mutual application of voltage and voltage frequency and their application boundaries. A combination of laws for regulation of the propulsion asynchronous electric motor has been selected in the paper. The combination ensures the widest operational range of the electric motor with high moment value at nominal sliding and due account of limitations on application of every used regulation law. The following mechanical characteristics family has been constructed for the propulsion asynchronous electric motor regulated in accordance with the proposed law: at nominal sliding, at critical sliding, at changeable sliding and without changes in voltage and frequency.

  13. Polyvinyl chloride as a multimodal tissue-mimicking material with tuned mechanical and medical imaging properties.

    Science.gov (United States)

    Li, Weisi; Belmont, Barry; Greve, Joan M; Manders, Adam B; Downey, Brian C; Zhang, Xi; Xu, Zhen; Guo, Dongming; Shih, Albert

    2016-10-01

    The mechanical and imaging properties of polyvinyl chloride (PVC) can be adjusted to meet the needs of researchers as a tissue-mimicking material. For instance, the hardness can be adjusted by changing the ratio of softener to PVC polymer, mineral oil can be added for lubrication in needle insertion, and glass beads can be added to scatter acoustic energy similar to biological tissue. Through this research, the authors sought to develop a regression model to design formulations of PVC with targeted mechanical and multimodal medical imaging properties. The design of experiment was conducted by varying three factors-(1) the ratio of softener to PVC polymer, (2) the mass fraction of mineral oil, and (3) the mass fraction of glass beads-and measuring the mechanical properties (elastic modulus, hardness, viscoelastic relaxation time constant, and needle insertion friction force) and the medical imaging properties [speed of sound, acoustic attenuation coefficient, magnetic resonance imaging time constants T 1 and T 2 , and the transmittance of the visible light at wavelengths of 695 nm (T λ695 ) and 532 nm (T λ532 )] on twelve soft PVC samples. A regression model was built to describe the relationship between the mechanical and medical imaging properties and the values of the three composition factors of PVC. The model was validated by testing the properties of a PVC sample with a formulation distinct from the twelve samples. The tested soft PVC had elastic moduli from 6 to 45 kPa, hardnesses from 5 to 50 Shore OOO-S, viscoelastic stress relaxation time constants from 114.1 to 191.9 s, friction forces of 18 gauge needle insertion from 0.005 to 0.086 N/mm, speeds of sound from 1393 to 1407 m/s, acoustic attenuation coefficients from 0.38 to 0.61 (dB/cm)/MHz, T 1 relaxation times from 426.3 to 450.2 ms, T 2 relaxation times from 21.5 to 28.4 ms, T λ695 from 46.8% to 92.6%, and T λ532 from 41.1% to 86.3%. Statistically significant factors of each property were

  14. Construction of three-dimensional liver tissue models by cell accumulation technique and maintaining their metabolic functions for long-term culture without medium change.

    Science.gov (United States)

    Matsuzawa, Atsushi; Matsusaki, Michiya; Akashi, Mitsuru

    2015-04-01

    Three-dimensional (3D) hepatocyte cultures have attracted much attention to obtain high biological functions of hepatocyte for pharmaceutical drug assessment. However, maintaining the high functions for over one month is still a key challenge although many approaches have been reported. In this study, we demonstrate for the first time simple and rapid construction of 3D-hepatocyte constructs by our cell accumulation technique and their high biological functions for one month, without any medium change. The human hepatocyte carcinoma (HepG2) cells were coated with ∼ 7 nm-sized extracellular matrix (ECM) films consisting of fibronectin (FN) and gelatin (G), and then incubated in cell culture insert to construct 3D-tissue constructs for 24 h. The thickness of obtained 3D-HepG2 constructs was easily controlled by altering seeding cell number and the maximum is over 100 μm. When a large volume of culture media was employed, the 3D-constructs showed higher mRNA expression of albumin and some cytochrome P450 (CYP) enzymes as compared to general two-dimensional (2D) culture. Surprisingly, their high cell viabilities (over 80%) and high mRNA expressions were successfully maintained without medium change for at least 27 days. These results demonstrate novel easy and rapid technique to construct 3D-human liver tissue models which can maintain their high functions and viability for 1 month without medium change. © 2014 Wiley Periodicals, Inc.

  15. An optical coherence tomography (OCT)-based air jet indentation system for measuring the mechanical properties of soft tissues

    Science.gov (United States)

    Huang, Yan-Ping; Zheng, Yong-Ping; Wang, Shu-Zhe; Chen, Zhong-Ping; Huang, Qing-Hua; He, Yong-Hong

    2009-01-01

    A novel noncontact indentation system with the combination of an air jet and optical coherence tomography (OCT) was presented in this paper for the quantitative measurement of the mechanical properties of soft tissues. The key idea of this method is to use a pressure-controlled air jet as an indenter to compress the soft tissue in a noncontact way and utilize the OCT signals to extract the deformation induced. This indentation system provides measurement and mapping of tissue elasticity for small specimens with high scanning speed. Experiments were performed on 27 silicone tissue-mimicking phantoms with different Young's moduli, which were also measured by uniaxial compression tests. The regression coefficient of the indentation force to the indentation depth (N mm-1) was used as an indicator of the stiffness of tissue under air jet indentation. Results showed that the stiffness coefficients measured by the current system correlated well with the corresponding Young's moduli obtained by conventional mechanical testing (r = 0.89, p < 0.001). Preliminary in vivo tests also showed that the change of soft tissue stiffness with and without the contraction of the underlying muscles in the hand could be differentiated by the current measurement. This system may have broad applications in tissue assessment and characterization where alterations of mechanical properties are involved, in particular with the potential of noncontact micro-indentation for tissues.

  16. Modeling the coupled mechanics, transport, and growth processes in collagen tissues.

    Energy Technology Data Exchange (ETDEWEB)

    Holdych, David J.; Nguyen, Thao D.; Klein, Patrick A.; in' t Veld, Pieter J.; Stevens, Mark Jackson

    2006-11-01

    The purpose of this project is to develop tools to model and simulate the processes of self-assembly and growth in biological systems from the molecular to the continuum length scales. The model biological system chosen for the study is the tendon fiber which is composed mainly of Type I collagen fibrils. The macroscopic processes of self-assembly and growth at the fiber scale arise from microscopic processes at the fibrillar and molecular length scales. At these nano-scopic length scales, we employed molecular modeling and simulation method to characterize the mechanical behavior and stability of the collagen triple helix and the collagen fibril. To obtain the physical parameters governing mass transport in the tendon fiber we performed direct numerical simulations of fluid flow and solute transport through an idealized fibrillar microstructure. At the continuum scale, we developed a mixture theory approach for modeling the coupled processes of mechanical deformation, transport, and species inter-conversion involved in growth. In the mixture theory approach, the microstructure of the tissue is represented by the species concentration and transport and material parameters, obtained from fibril and molecular scale calculations, while the mechanical deformation, transport, and growth processes are governed by balance laws and constitutive relations developed within a thermodynamically consistent framework.

  17. Additively Manufactured Scaffolds for Bone Tissue Engineering and the Prediction of their Mechanical Behavior: A Review.

    Science.gov (United States)

    Zhang, Xiang-Yu; Fang, Gang; Zhou, Jie

    2017-01-10

    Additive manufacturing (AM), nowadays commonly known as 3D printing, is a revolutionary materials processing technology, particularly suitable for the production of low-volume parts with high shape complexities and often with multiple functions. As such, it holds great promise for the fabrication of patient-specific implants. In recent years, remarkable progress has been made in implementing AM in the bio-fabrication field. This paper presents an overview on the state-of-the-art AM technology for bone tissue engineering (BTE) scaffolds, with a particular focus on the AM scaffolds made of metallic biomaterials. It starts with a brief description of architecture design strategies to meet the biological and mechanical property requirements of scaffolds. Then, it summarizes the working principles, advantages and limitations of each of AM methods suitable for creating porous structures and manufacturing scaffolds from powdered materials. It elaborates on the finite-element (FE) analysis applied to predict the mechanical behavior of AM scaffolds, as well as the effect of the architectural design of porous structure on its mechanical properties. The review ends up with the authors' view on the current challenges and further research directions.

  18. PHYSICAL AND MECHANICAL PROPERTIES OF BLACK WOOD (EBONY AS A CONSTRUCTION MATERIAL

    Directory of Open Access Journals (Sweden)

    Fengky Satria Yoresta

    2015-01-01

    Full Text Available This research is aimed to determine physical and mechanical properties of Ebony wood as a construction material. The physical and mechanical properties test is conducted based on ASTM D 143-94 code. The mean value of moisture content and specific gravity of Ebony wood is obtained 12,90% and 0,92 gr.cm-3 respectively. Meanwhile MOE, bending strength, compressive strength parallel to grain, shear strength, and tensile strength parallel to grain are 180.425,87 kg.cm-2; 1656,22 kg.cm-2; 861,55 kg.cm-2; 119,61 kg.cm-2; dan 2.319,03 kg.cm-2 respectively. Based on the test results, it can be concluded that Ebony wood is classified to Strength Class I due to PKKI 1961, so it can be recommended for use in heavy construction such as bridge and building structures   Penelitian ini bertujuan menentukan sifat fisis dan mekanis kayu  Ebony sebagai material konstruksi. Pengujian sifat fisis dan mekanis dilakukan berdasarkan standar ASTM D 143-94. -3Nilai kadar air rata-rata kayu Ebony diperoleh sebesar 12,90% dan berat jenis 0,92 gr.cm . Sementara nilai rata-rata MOE, kuat lentur, kuat tekan sejajar serat, kuat geser, dan kuat tarik -2 -2 -2sejajar serat berturut-turut adalah 180.425,87 kg.cm ; 1656,22 kg.cm ; 861,55 kg.cm ; -2 -2119,61 kg.cm ; dan 2.319,03 kg.cm . Berdasarkan hasil penelitian dapat disimpulkan bahwa kayu Ebony tergolong kelas kuat I menurut PKKI 1961, sehingga dapat direkomendasikan untuk digunakan pada konstruksi-konstruksi berat seperti jembatan dan struktur bangunan.   REFERENCES Aghayere A & Jason V. 2007. Structural Wood Design: A Practice-Oriented Approach Using the ASD Method. John Wiley & Sons, Inc., New Jersey Boen T. 2009. Constructing Seismic Resistant Masonry Houses in Indonesia. United Nation. Chauf KA. 2005. Karakteristik Mekanik Kayu Kamper sebagai Bahan Konstruksi. Majalah Ilmiah MEKTEK . Vol 7 : 41-47. Dolan JD. 2004. Timber Structures. Pp 628-669 in Wai FC & Eric ML (Eds Handbook of Structural Engineering – 2nd

  19. Characterizing tissue stiffness at the tip of a rigid needle using an opto-mechanical force sensor (Conference Presentation)

    Science.gov (United States)

    Beekmans, Steven V.; Iannuzzi, Davide; van den Dobbelsteen, John J.

    2016-03-01

    Each year, in the Netherlands alone, more than 50.000 percutaneous procedures are performed for treatment or for removal of tissue from possibly diseased organs, of which 30% return non-diagnostic due to erroneous needle targeting, often as a result of non-homogeneity of the penetrated tissue. In this study, we aim to facilitate needle targeting by assessing the tissue in front of the needle based on its mechanical properties. A probe that can identify tissues via real-time measurements of their mechanical properties is placed at the tip of the needle. The probe, actuated by a remote system at the distal part of the needle, employs the bending of a micro-machined cantilever fabricated on top of an optical fiber. The displacement of the cantilever, imposed by pressing a micro-bead (r = 75 µm) glued at the tip of the cantilever against the tissue, is interrogated by Fabry-Pérot interferometry and converted to force acted on the tissue in real-time. The force transducer is able to perform in harsh environments due to its monolithic design and all-optical working principle. Using our setup, load-indentation curves were obtained during needle insertion in several gelatin-based specimens. We demonstrate the ability of our device to detect and quantify layers of varying stiffness and to successfully locate tissue boundaries in animal tissue embedded in gelatin. Furthermore, a diagnostic measurement can be made by quantifying intra-organ tissue stiffness at the needle target location.

  20. Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child

    Directory of Open Access Journals (Sweden)

    Shihai Cui

    2015-01-01

    Full Text Available Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters.

  1. Alteration of local adipose tissue trace element homeostasis as a possible mechanism of obesity-related insulin resistance.

    Science.gov (United States)

    Tinkov, Alexey A; Sinitskii, Anton I; Popova, Elizaveta V; Nemereshina, Olga N; Gatiatulina, Evgenia R; Skalnaya, Margarita G; Skalny, Anatoly V; Nikonorov, Alexandr A

    2015-09-01

    The mechanisms of association between obesity and the related metabolic disturbances in general and insulin resistance in particular are extensively studied. Taking into account a key role of adipose tissue insulin resistance in the development of systemic obesity-related insulin resistance, the estimation of mechanisms linking increased adiposity and impaired insulin signaling in adipocytes will allow to develop novel prophylactic and therapeutic approaches to treatment of these states. A number of trace elements like chromium, zinc, and vanadium have been shown to take part in insulin signaling via various mechanisms. Taking into account a key role of adipocyte in systemic carbohydrate homeostasis it can be asked if trace element homeostasis in adipose tissue may influence regulatory mechanisms of glucose metabolism. We hypothesize that caloric excess through currently unknown mechanisms results in decreased chromium, vanadium, and zinc content in adipocytes. Decreased content of trace elements in the adipose tissue causes impairment of intra-adipocyte insulin signaling subsequently leading to adipose tissue insulin resistance. The latter significantly contributes to systemic insulin resistance and further metabolic disruption in obesity. It is also possible that decreased adipose tissue trace element content is associated with dysregulation of insulin-sensitizing and proinflammatory adipokines also leading to insulin resistance. We hypothesize that insulin resistance and adipokine dysbalance increase the severity of obesity subsequently aggravating alteration of adipose tissue trace element balance. Single indications of high relative adipose tissue trace element content, decreased Cr, V, and Zn content in obese adipose tissue, and tight association between fat tissue chromium, vanadium, and zinc levels and metabolic parameters in obesity may be useful for hypothesis validation. If our hypothesis will be confirmed by later studies, adipose tissue chromium

  2. Mechanisms of Tolerance to Parental Parathyroid Tissue when Combined with Human Allogeneic Thymus Transplantation

    Science.gov (United States)

    Chinn, Ivan K.; Olson, John A.; Skinner, Michael A.; McCarthy, Elizabeth A.; Gupton, Stephanie E.; Chen, Dong-Feng; Bonilla, Francisco A.; Roberts, Robert L.; Kanariou, Maria G.; Devlin, Blythe H.; Markert, M. Louise

    2010-01-01

    Background The induction of tolerance toward third-party solid organ grafts with allogeneic thymus tissue transplantation has not been previously demonstrated in human subjects. Objective Infants with complete DiGeorge anomaly (having neither thymus nor parathyroid function) were studied for conditions and mechanisms required for the development of tolerance to third-party solid organ tissues. Methods Four infants who met criteria received parental parathyroid with allogeneic thymus transplantation and were studied. Results Two of three survivors showed function of both grafts but subsequently lost parathyroid function. They demonstrated alloreactivity against the parathyroid donor in mixed lymphocyte cultures. For these 2 recipients, parathyroid donor HLA class II alleles were mismatched with the recipient and thymus. MHC class II tetramers confirmed the presence of recipient CD4+ T cells with specificity towards a mismatched parathyroid donor class II allele. The third survivor has persistent graft function and lacks alloreactivity towards the parathyroid donor. All parathyroid donor class II alleles were shared with either the recipient or the thymus graft, with minor differences between the parathyroid (HLA-DRB1*1104) and thymus (HLA-DRB1*1101). Tetramer analyses detected recipient T cells specific for the parathyroid HLA-DRB1*1104 allele. Alloreactivity towards the parathyroid donor was restored with low-doses of IL-2. Conclusion Tolerance toward parathyroid grafts in combined parental parathyroid and allogeneic thymus transplantation requires matching of thymus tissue to parathyroid HLA class II alleles to promote negative selection and suppression of recipient T cells that have alloreactivity toward the parathyroid grafts. This matching strategy may be applied toward tolerance induction in future combined thymus and solid organ transplantation efforts. PMID:20832849

  3. Molecular mechanism of hypoxia-induced chondrogenesis and its application in in vivo cartilage tissue engineering.

    Science.gov (United States)

    Duval, Elise; Baugé, Catherine; Andriamanalijaona, Rina; Bénateau, Hervé; Leclercq, Sylvain; Dutoit, Soizic; Poulain, Laurent; Galéra, Philippe; Boumédiene, Karim

    2012-09-01

    Cartilage engineering is one of the most challenging issue in regenerative medicine, due to its limited self-ability to repair. Here, we assessed engineering of cartilage tissue starting from human bone marrow (hBM) stem cells under hypoxic environment and delineated the mechanism whereby chondrogenesis could be conducted without addition of exogenous growth factors. hBM stem cells were cultured in alginate beads and chondrogenesis was monitored by chondrocyte phenotypic markers. Activities and roles of Sox and HIF-1α transcription factors were investigated with complementary approaches of gain and loss of function and provided evidences that HIF-1α is essential for hypoxic induction of chondrogenesis. Thereafter, hBM cells and human articular chondrocytes (HAC) underwent chondrogenesis by 3D and hypoxic culture for 7 days or by ectopic expression of HIF-1α. After subcutaneous implantation of 3 weeks into athymic mice, tissue analysis showed that hypoxia or HIF-1α overexpression is effective and sufficient to induce chondrocyte phenotype in hBM cells, without use of exogenous growth factors. Therefore, this study brings interesting data for a simple and affordable system in biotechnology of cartilage engineering. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Mechanical properties and biocompatibility of porous titanium scaffolds for bone tissue engineering.

    Science.gov (United States)

    Chen, Yunhui; Frith, Jessica Ellen; Dehghan-Manshadi, Ali; Attar, Hooyar; Kent, Damon; Soro, Nicolas Dominique Mathieu; Bermingham, Michael J; Dargusch, Matthew S

    2017-11-01

    Synthetic scaffolds are a highly promising new approach to replace both autografts and allografts to repair and remodel damaged bone tissue. Biocompatible porous titanium scaffold was manufactured through a powder metallurgy approach. Magnesium powder was used as space holder material which was compacted with titanium powder and removed during sintering. Evaluation of the porosity and mechanical properties showed a high level of compatibility with human cortical bone. Interconnectivity between pores is higher than 95% for porosity as low as 30%. The elastic moduli are 44.2GPa, 24.7GPa and 15.4GPa for 30%, 40% and 50% porosity samples which match well to that of natural bone (4-30GPa). The yield strengths for 30% and 40% porosity samples of 221.7MPa and 117MPa are superior to that of human cortical bone (130-180MPa). In-vitro cell culture tests on the scaffold samples using Human Mesenchymal Stem Cells (hMSCs) demonstrated their biocompatibility and indicated osseointegration potential. The scaffolds allowed cells to adhere and spread both on the surface and inside the pore structures. With increasing levels of porosity/interconnectivity, improved cell proliferation is obtained within the pores. It is concluded that samples with 30% porosity exhibit the best biocompatibility. The results suggest that porous titanium scaffolds generated using this manufacturing route have excellent potential for hard tissue engineering applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Rectification of pulsatile stress on soft tissues: a mechanism for normal-pressure hydrocephalus

    Science.gov (United States)

    Jalikop, Shreyas; Hilgenfeldt, Sascha

    2011-11-01

    Hydrocephalus is a pathological condition of the brain that occurs when cerebrospinal fluid (CSF) accumulates excessively in the brain cavities, resulting in compression of the brain parenchyma. Counter-intuitively, normal-pressure hydrocephalus (NPH) does not show elevated pressure differences across the compressed parenchyma. We investigate the effects of nonlinear tissue mechanics and periodic driving in this system. The latter is due to the cardiac cycle, which provides significant intracranial pressure and volume flow rate fluctuations. Nonlinear rectification of the periodic driving within a model of fluid flow in poroelastic material can lead to compression or expansion of the parenchyma, and this effect does not rely on changes in the mean intracranial pressure. The rectification effects can occur gradually over several days, in agreement with clinical studies of NPH.

  6. Intramuscular connective tissue differences in spastic and control muscle: a mechanical and histological study.

    Directory of Open Access Journals (Sweden)

    Marije de Bruin

    Full Text Available Cerebral palsy (CP of the spastic type is a neurological disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks. Secondary to the spasticity, muscle adaptation is presumed to contribute to limitations in the passive range of joint motion. However, the mechanisms underlying these limitations are unknown. Using biopsies, we compared mechanical as well as histological properties of flexor carpi ulnaris muscle (FCU from CP patients (n = 29 and healthy controls (n = 10. The sarcomere slack length (mean 2.5 µm, SEM 0.05 and slope of the normalized sarcomere length-tension characteristics of spastic fascicle segments and single myofibre segments were not different from those of control muscle. Fibre type distribution also showed no significant differences. Fibre size was significantly smaller (1933 µm2, SEM 190 in spastic muscle than in controls (2572 µm2, SEM 322. However, our statistical analyses indicate that the latter difference is likely to be explained by age, rather than by the affliction. Quantities of endomysial and perimysial networks within biopsies of control and spastic muscle were unchanged with one exception: a significant thickening of the tertiary perimysium (3-fold, i.e. the connective tissue reinforcement of neurovascular tissues penetrating the muscle. Note that this thickening in tertiary perimysium was shown in the majority of CP patients, however a small number of patients (n = 4 out of 23 did not have this feature. These results are taken as indications that enhanced myofascial loads on FCU is one among several factors contributing in a major way to the aetiology of limitation of movement at the wrist in CP and the characteristic wrist position of such patients.

  7. On the toxicity and transport mechanisms of cisplatin in kidney tissues in comparison to a gold-based cytotoxic agent

    NARCIS (Netherlands)

    Spreckelmeyer, Sarah; Estrada Ortiz, Natalia; Prins, Gerian; van der Zee, Margot; Gammelgaard, Bente; Sturup, Stefan; de Graaf, Inge; Groothuis, G. M. M.; Casini, Angela

    2017-01-01

    Mechanisms of toxicity and cellular transport of anticancer metallodrugs, including platinum-based agents, have not yet been fully elucidated. Here, we studied the toxic effects and accumulation mechanisms of cisplatin in healthy rat kidneys ex vivo, using the Precision Cut Tissue Slices (PCTS)

  8. Mechanical properties of hot mix asphalt made with recycled aggregates from reclaimed construction and demolition debris

    Directory of Open Access Journals (Sweden)

    Taibo, J.

    2007-03-01

    Full Text Available The mix design for asphalt mixtures containing recycled aggregates from construction and demolition debris was evaluated. The tests conducted to characterize the mechanical behaviour of these mixtures showed that the mechanical properties of mixtures with recycled and virgin aggregate are similar. The asphalt mixtures containing recycled aggregate proved to have lower resistance to water action. Nonetheless, recycled aggregate was found to be potentially usable in asphalt mixtures if higher quality materials are selected and such low resistance is corrected. This will call for expanding upon the preliminary work described in the present article.En este trabajo se dosificaron mezclas bituminosas fabricadas con áridos reciclados de residuos de construcción y demolición. Se realizaron una serie de ensayos que permitieron caracterizar el comportamiento mecánico de estas mezclas. Los parámetros mecánicos de las mezclas con áridos reciclados son similares a los de las mezclas fabricadas únicamente con áridos naturales de cantera. Sin embargo, las mezclas bituminosas con áridos reciclados tuvieron un mal comportamiento frente a la disminución de la resistencia por pérdida de cohesión por la acción del agua. No obstante, mediante la selección de materiales de mejor calidad y corrección de este mal comportamiento, existen posibilidades de utilizar áridos reciclados en mezclas bituminosas. Para ello será necesario ampliar la primera aproximación realizada en este artículo.

  9. Physical and Mechanical Characterization of Sugarcane Bagasse Particleboards for Civil Construction

    Directory of Open Access Journals (Sweden)

    Rosane Battistelle

    2016-12-01

    Full Text Available In the worldwide market of particleboard production, the use of alternative raw materials is increasing, due to high demand and lack of traditional raw material, despite efforts of reforestation. In Brazil, the main agricultural commodity is sugarcane due to the copious production of sugar and ethanol. In the state of São Paulo alone approximately 140 million tons of sugarcane bagasse are produced every year, from which around 70% is burned for energy production, not adding value to the residue and generating pollution to the environment; and the other 30% is sold for composting. The objective of this work is to add value to the sugarcane bagasse by using it as a raw material for particleboard production to be employed as flooring in the area of civil construction. To achieve this, the present research characterized the physical and mechanical characteristics of the particleboards with the following alternative raw materials: sugarcane bagasse and leaves of bamboo. Particleboards were produced to reach high density (0.8g/cm3 using the resin (bi-component polyurethane castor oil. Tests for abrasion, roughness and resistance to denting and wear (Janka hardness verified that the addition of leaves of bamboo in the mixtures, contrary to what was expected, did not confer a greater degree of resistance to the particleboards. Lastly, the results showed that sugarcane bagasse is a viable raw material alternative for the production of particleboards, intended to be used as products and flooring.

  10. Biological mechanisms associated with triazophos (TAP) removal by horizontal subsurface flow constructed wetlands (HSFCW)

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Juan; Feng, Yuqin; Dai, Yanran; Cui, Naxin [State Key Laboratory of Pollution Control and ResourceReuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092 (China); Anderson, Bruce [Department of Civil Engineering, Queen' s University, Kingston K7L3N6 (Canada); Cheng, Shuiping, E-mail: shpcheng@tongji.edu.cn [State Key Laboratory of Pollution Control and ResourceReuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092 (China)

    2016-05-15

    Triazophos (TAP) is a widely used pesticide that is easily accumulated in the environment due to its relatively high stability: this accumulation from agricultural runoff results in potential hazards to aquatic ecosystems. Constructed wetlands are generally considered to be an effective technology for treating TAP polluted surface water. However, knowledge about the biological mechanisms of TAP removal is still lacking. This study investigates the responses of a wetland plant (Canna indica), substrate enzymes and microbial communities in bench-scale horizontal subsurface-flow constructed wetlands (HSCWs) loaded with different TAP concentrations (0, 0.1, 0.5 and 5 mg·L{sup −1}). The results indicate that TAP stimulated the activities of superoxide dismutase (SOD) and peroxidase (POD) in the roots of C. indica. The highest TAP concentrations significantly inhibited photosynthetic activities, as shown by a reduced effective quantum yield of PS II (Φ{sub PSII}) and lower electron transport rates (ETR). However, interestingly, the lower TAP loadings exhibited some favorable effects on these two variables, suggesting that C. indica is a suitable species for use in wetlands designed for treatment of low TAP concentrations. Urease and alkaline phosphatase (ALP) in the wetland substrate were activated by TAP. Two-way ANOVA demonstrated that urease activity was influenced by both the TAP concentrations and season, while acidphosphatase (ACP) only responded to seasonal variations. Analysis of high throughput sequencing of 16S rRNA revealed seasonal variations in the microbial community structure of the wetland substrate at the phylum and family levels. In addition, urease activity had a greater correlation with the relative abundance of some functional microbial groups, such as the Bacillaceae family, and the ALP and ACP may be influenced by the plant more than substrate microbial communities. - Highlights: • Physiological responses of the wetland plant to triazophos

  11. Biological mechanisms associated with triazophos (TAP) removal by horizontal subsurface flow constructed wetlands (HSFCW)

    International Nuclear Information System (INIS)

    Wu, Juan; Feng, Yuqin; Dai, Yanran; Cui, Naxin; Anderson, Bruce; Cheng, Shuiping

    2016-01-01

    Triazophos (TAP) is a widely used pesticide that is easily accumulated in the environment due to its relatively high stability: this accumulation from agricultural runoff results in potential hazards to aquatic ecosystems. Constructed wetlands are generally considered to be an effective technology for treating TAP polluted surface water. However, knowledge about the biological mechanisms of TAP removal is still lacking. This study investigates the responses of a wetland plant (Canna indica), substrate enzymes and microbial communities in bench-scale horizontal subsurface-flow constructed wetlands (HSCWs) loaded with different TAP concentrations (0, 0.1, 0.5 and 5 mg·L −1 ). The results indicate that TAP stimulated the activities of superoxide dismutase (SOD) and peroxidase (POD) in the roots of C. indica. The highest TAP concentrations significantly inhibited photosynthetic activities, as shown by a reduced effective quantum yield of PS II (Φ PSII ) and lower electron transport rates (ETR). However, interestingly, the lower TAP loadings exhibited some favorable effects on these two variables, suggesting that C. indica is a suitable species for use in wetlands designed for treatment of low TAP concentrations. Urease and alkaline phosphatase (ALP) in the wetland substrate were activated by TAP. Two-way ANOVA demonstrated that urease activity was influenced by both the TAP concentrations and season, while acidphosphatase (ACP) only responded to seasonal variations. Analysis of high throughput sequencing of 16S rRNA revealed seasonal variations in the microbial community structure of the wetland substrate at the phylum and family levels. In addition, urease activity had a greater correlation with the relative abundance of some functional microbial groups, such as the Bacillaceae family, and the ALP and ACP may be influenced by the plant more than substrate microbial communities. - Highlights: • Physiological responses of the wetland plant to triazophos loads were

  12. Manipulation of mechanical compliance of elastomeric PGS by incorporation of halloysite nanotubes for soft tissue engineering applications.

    Science.gov (United States)

    Chen, Qi-Zhi; Liang, Shu-Ling; Wang, Jiang; Simon, George P

    2011-11-01

    Poly (glycerol sebacate) (PGS) is a promising elastomer for use in soft tissue engineering. However, it is difficult to achieve with PGS a satisfactory balance of mechanical compliance and degradation rate that meet the requirements of soft tissue engineering. In this work, we have synthesised a new PGS nanocomposite system filled with halloysite nanotubes, and mechanical properties, as well as related chemical characters, of the nanocomposites were investigated. It was found that the addition of nanotubular halloysite did not compromise the extensibility of material, compared with the pure PGS counterpart; instead the elongation at rupture was increased from 110 (in the pure PGS) to 225% (in the 20 wt% composite). Second, Young's modulus and resilience of 3-5 wt% composites were ∼0.8 MPa and >94% respectively, remaining close to the level of pure PGS which is desired for applications in soft tissue engineering. Third, an important feature of the 1-5 wt% composites was their stable mechanical properties over an extended period, which could allow the provision of reliable mechanical support to damaged tissues during the lag phase of the healing process. Finally, the in vitro study indicated that the addition of halloysite slowed down the degradation rate of the composites. In conclusion, the good compliance, enhanced stretchability, stable mechanical behavior over an extended period, and reduced degradation rates make the 3-5 wt% composites promising candidates for application in soft tissue engineering. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. The healing of bony defects by cell-free collagen-based scaffolds compared to stem cell-seeded tissue engineered constructs.

    LENUS (Irish Health Repository)

    Lyons, Frank G

    2010-12-01

    One of the key challenges in tissue engineering is to understand the host response to scaffolds and engineered constructs. We present a study in which two collagen-based scaffolds developed for bone repair: a collagen-glycosaminoglycan (CG) and biomimetic collagen-calcium phosphate (CCP) scaffold, are evaluated in rat cranial defects, both cell-free and when cultured with MSCs prior to implantation. The results demonstrate that both cell-free scaffolds showed excellent healing relative to the empty defect controls and somewhat surprisingly, to the tissue engineered (MSC-seeded) constructs. Immunological analysis of the healing response showed higher M1 macrophage activity in the cell-seeded scaffolds. However, when the M2 macrophage response was analysed, both groups (MSC-seeded and non-seeded scaffolds) showed significant activity of these cells which are associated with an immunomodulatory and tissue remodelling response. Interestingly, the location of this response was confined to the construct periphery, where a capsule had formed, in the MSC-seeded groups as opposed to areas of new bone formation in the non-seeded groups. This suggests that matrix deposited by MSCs during in vitro culture may adversely affect healing by acting as a barrier to macrophage-led remodelling when implanted in vivo. This study thus improves our understanding of host response in bone tissue engineering.

  14. Attention and working memory: two basic mechanisms for constructing temporal experiences

    OpenAIRE

    Marchetti, Giorgio

    2014-01-01

    Various kinds of observations show that the ability of human beings to both consciously relive past events – episodic memory – and conceive future events, entails an active process of construction. This construction process also underpins many other important aspects of conscious human life, such as perceptions, language, and conscious thinking. This article provides an explanation of what makes the constructive process possible and how it works. The process mainly relies on attentional activ...

  15. Statistical model for the mechanical behavior of the tissue engineering non-woven fibrous matrices under large deformation.

    Science.gov (United States)

    Rizvi, Mohd Suhail; Pal, Anupam

    2014-09-01

    The fibrous matrices are widely used as scaffolds for the regeneration of load-bearing tissues due to their structural and mechanical similarities with the fibrous components of the extracellular matrix. These scaffolds not only provide the appropriate microenvironment for the residing cells but also act as medium for the transmission of the mechanical stimuli, essential for the tissue regeneration, from macroscopic scale of the scaffolds to the microscopic scale of cells. The requirement of the mechanical loading for the tissue regeneration requires the fibrous scaffolds to be able to sustain the complex three-dimensional mechanical loading conditions. In order to gain insight into the mechanical behavior of the fibrous matrices under large amount of elongation as well as shear, a statistical model has been formulated to study the macroscopic mechanical behavior of the electrospun fibrous matrix and the transmission of the mechanical stimuli from scaffolds to the cells via the constituting fibers. The study establishes the load-deformation relationships for the fibrous matrices for different structural parameters. It also quantifies the changes in the fiber arrangement and tension generated in the fibers with the deformation of the matrix. The model reveals that the tension generated in the fibers on matrix deformation is not homogeneous and hence the cells located in different regions of the fibrous scaffold might experience different mechanical stimuli. The mechanical response of fibrous matrices was also found to be dependent on the aspect ratio of the matrix. Therefore, the model establishes a structure-mechanics interdependence of the fibrous matrices under large deformation, which can be utilized in identifying the appropriate structure and external mechanical loading conditions for the regeneration of load-bearing tissues. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. The results of the investigations on rock mechanics in HDB-9-11 boreholes and update of the rock mechanical model around the Horonobe URL construction area

    International Nuclear Information System (INIS)

    Sanada, Hiroyuki; Niunoya, Sumio; Matsui, Hiroya

    2008-09-01

    Horonobe URL (Underground Research Laboratory) Project is conducted at Horonobe-cho, Teshio-gun, Hokkaido. This research report shows the result of the rock mechanical investigations which have been carried out from 2004 to 2005 as a part of the project. The objectives of the rock mechanical investigation are as follows: To obtain the data which were necessary for construction design of URL. To confirm the distribution of rock mechanical properties in and around URL construction area. The results of the investigations are summarized as follows: 1) Variation and values of depth direction of physical and mechanical properties in the laboratory construction area corresponded approximately to the results obtained from the rock mechanical investigations of HDB-1-8. 2) The major redesign had been not had about physical and mechanical properties in the laboratory construction area being able to divide into three zones and length of its own zone in updating rock mechanical model. 3) From the results of initial stress measured by hydraulic fracturing, the results that the direction of the maximum principle stress is E-W was no different from results obtained from the investigations of HDB-1-8, but the magnitude correlation among maximum, minimum principle stress and overburden pressure measured around G.L.-927 m showed different trends compared with the results of HDB-1-8. 4) Diatomaceous mudstone was yielded under isotropic compression. Cam-clay model as constitutive law of diatomaceous mudstone should be used for tunnel excavation analysis. 5) Uniaxial compression strength of rock saturated under saline water is larger than that of saturated under freshwater. Poisson's ratio of rock saturated under saline water is smaller than that of saturated under saline water. 6) The effective confining pressure increases with the equivalent opening width and permeability decreases. 7) The value of principle stress obtained from DSCA method is larger than that obtained from hydraulic

  17. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low

    Energy Technology Data Exchange (ETDEWEB)

    Kadhim, Munira A

    2012-08-22

    The above studies will provide fundamental mechanistic information relating genetic predisposition to important low dose phenomena, and will aid in the development of Department of Energy policy, as well as radiation risk policy for the public and the workplace. We believe the proposed studies accurately reflect the goals of the DOE low dose program. To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e. less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these "non-targeted responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate non-targeted effects of ionizing radiation with a focus on the induction of genomic instability (GI) in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/CaH and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition in these models on genomic instability. We will specifically focus on the effects of low doses of low LET radiation, down to the dose of 10mGy (0.01Gy) X-rays. Using conventional X-ray and we will be able to assess the role of genetic variation under various conditions at a range of doses down to the very low dose of 0.01Gy. Irradiations will be carried out using facilities in routine operation for such studies. Mechanistic studies of instability in different cell

  18. Mesh construction for the 2-dimensional computational fracture mechanics using the I-DEAS

    International Nuclear Information System (INIS)

    Kim, Jong Wook; Kim, Tae Wan; Park, Keun Bae

    2000-09-01

    Recently research activities have been reported regarding the generation of the input data for the crack problems at a minimum of effort utilizing the general characteristics of the finite element modeling technique. Several automatic FE mesh generation methods for the cracked structure of particular geometries and boundary conditions have been proposed by using commercial codes or developing in-house programs. In general, development of software to deal with special crack problem can maximize the efficiency and accuracy for a specific environment. However, applicable range of such scheme is usually very restricted and new program should be formed in each case. On the other hand, commercial codes can be used for the automatic mesh generation of variety of geometries, but with an additional effort to accomodate the singular element for the cracked-body analysis. In the present study, a procedure for the generation of input data for the optimized computational fracture mechanics is developed as a series of effort to establish the structural integrity evaluation procedure of SMART reactor vessel assembly. Input data for the finite element analysis are prepared using the commercial code I-DEAS. The midpoint nodes near the crack front are shifted at the quarter-points. The complete finite element model generated is given to another commercial finite element code ABAQUS for the stress analysis. The stress intensity factors are calculated using the J-integral method. To demonstrate the validation of the present procedure, double-edge crack in a plate subjected to uniform tension is solved, and the effects of mesh construction are discussed in detail. The structural integrity evaluation procedure through the 2-D crack modeling is then established

  19. Relationships of the internodal distance of biological tissue with its sound velocity and attenuation at high frequency in doublet mechanics

    Science.gov (United States)

    Cheng, Kai-Xuan; Wu, Rong-Rong; Liu, Xiao-Zhou; Liu, Jie-Hui; Gong, Xiu-Fen; Wu, Jun-Ru

    2015-04-01

    In view of the discrete characteristics of biological tissue, doublet mechanics has demonstrated its advantages in the mathematic description of tissue in terms of high frequency (> 10 MHz) ultrasound. In this paper, we take human breast biopsies as an example to study the influence of the internodal distance, a microscope parameter in biological tissue in doublet mechanics, on the sound velocity and attenuation by numerical simulation. The internodal distance causes the sound velocity and attenuation in biological tissue to change with the increase of frequency. The magnitude of such a change in pathological tissue is distinctly different from that in normal tissue, which can be used to differentiate pathological tissue from normal tissue and can depict the diseased tissue structure by obtaining the sound and attenuation distribution in the sample at high ultrasound frequency. A comparison of sensitivity between the doublet model and conventional continuum model is made, indicating that this is a new method of characterizing ultrasound tissue and diagnosing diseases. Project supported by the National Basic Research Program of China (Grant Nos. 2012CB921504 and 2011CB707902), the National Natural Science Foundation of China (Grant No. 11274166), the Fundamental Research Funds for the Central Universities, China (Grant Nos. 1113020403 and 1101020402), the State Key Laboratory of Acoustics, Chinese Academy of Sciences (Grant No. SKLA201401), the China Postdoctoral Science Foundation (Grant No. 2013M531313), the Priority Academic Program Development of Jiangsu Provincial Higher Education Institutions and Scientific Research Foundation for Returned Overseas Chinese Scholars, State Education Ministry, and the Project of Interdisciplinary Center of Nanjing University, China (Grant No. NJUDC2012004).

  20. Tracking mechanical and morphological dynamics of regenerating Hydra tissue fragments using a two fingered micro-robotic hand

    Science.gov (United States)

    Veschgini, M.; Gebert, F.; Khangai, N.; Ito, H.; Suzuki, R.; Holstein, T. W.; Mae, Y.; Arai, T.; Tanaka, M.

    2016-03-01

    Regeneration of a tissue fragment of freshwater polyp Hydra is accompanied by significant morphological fluctuations, suggesting the generation of active forces. In this study, we utilized a two fingered micro-robotic hand to gain insights into the mechanics of regenerating tissues. Taking advantage of a high force sensitivity (˜1 nN) of our micro-hand, we non-invasively acquired the bulk elastic modulus of tissues by keeping the strain levels low (ɛ < 0.15). Moreover, by keeping the strain at a constant level, we monitored the stress relaxation of the Hydra tissue and determined both viscous modulus and elastic modulus simultaneously, following a simple Maxwell model. We further investigated the correlation between the frequency of force fluctuation and that of morphological fluctuation by monitoring one "tweezed" tissue and the other "intact" tissue at the same time. The obtained results clearly indicated that the magnitude and periodicity of the changes in force and shape are directly correlated, confirming that our two fingered micro-hand can precisely quantify the mechanics of soft, dynamic tissue during the regeneration and development in a non-invasive manner.

  1. How one can construct a consistent relativistic quantum mechanics on the base of a relativistic wave equation

    International Nuclear Information System (INIS)

    Gavrilov, S.P.; Gitman, D.M.

    2000-01-01

    Full text follows: There is a common opinion that the construction of a consistent relativistic quantum mechanics on the base of a relativistic wave equation meets well-known difficulties related to the existence of infinite number of negative energy levels, to the existence of negative vector norms, and so on, which may be only solved in a second-quantized theory, see, for example, two basic papers devoted to the problem L.Foldy, S.Wouthuysen, Phys. Rep.78 (1950) 29; H.Feshbach, F.Villars, Rev. Mod. Phys. 30 (1958) 24, whose arguments are repeated in all handbooks in relativistic quantum theory. Even Dirac trying to solve the problem had turned last years to infinite-component relativistic wave equations, see P.A.M. Dirac, Proc. R. Soc. London, A328 (1972) 1. We believe that a consistent relativistic quantum mechanics may be constructed on the base of an extended (charge symmetric) equation, which unite both a relativistic wave equation for a particle and for an antiparticle. We present explicitly the corresponding construction, see for details hep-th/0003112. We support such a construction by two demonstrations: first, in course of a careful canonical quantization of the corresponding classical action of a relativistic particle we arrive just to such a consistent quantum mechanics; second, we demonstrate that a reduction of the QFT of a corresponding field (scalar, spinor, etc.) to one-particle sector, if such a reduction may be done, present namely this quantum mechanics. (author)

  2. Life-long endurance running is associated with reduced glycation and mechanical stress in connective tissue

    DEFF Research Database (Denmark)

    Couppé, Christian; Svensson, René B; Grosset, Jean-Francois

    2014-01-01

    counteract the aging process in connective tissue by reducing age-related accumulation of AGEs. This may not only benefit skin and tendon but also other long-lived protein tissues in the body. Furthermore, it appears that endurance running yields tendon tissue hypertrophy that may serve to lower the stress...

  3. Use of Leeds-Keio connective tissue prosthesis (L-K CTP) for reconstruction of deficient extensor mechanism with total knee replacement.

    Science.gov (United States)

    Sherief, Tamer I; Naguib, Ashraf M; Sefton, Graham K

    2005-08-01

    This study was carried out in order to assess the results of reconstruction of a deficient extensor mechanism in the presence of a total knee replacement (TKR) using the Leeds-Keio Connective Tissue Prosthesis (L-K CTP). The L-K CTP is available as flat tapes constructed from polyester in an open weave structure. It was used to reinforce and reconstruct the extensor mechanism, which was deficient in three patients who had undergone total knee replacement or were about to undergo total knee replacement. Two cases had extensor mechanism deficiency as a complication following total knee replacement while the third case had extensor mechanism deficiency at the time of the primary knee replacement. The average follow-up was 2 years (range of follow up was 12 to 48 months). All three cases showed good results with no extension lag and good range of movement at follow up. The use of L-K CTP for reconstruction of the knee extensor mechanism offers a good option for the management of the uncommon but difficult problem of extensor mechanism deficiency in patients with a total knee replacement.

  4. Computer-aided multiple-head 3D printing system for printing of heterogeneous organ/tissue constructs.

    Science.gov (United States)

    Jung, Jin Woo; Lee, Jung-Seob; Cho, Dong-Woo

    2016-02-22

    Recently, much attention has focused on replacement or/and enhancement of biological tissues via the use of cell-laden hydrogel scaffolds with an architecture that mimics the tissue matrix, and with the desired three-dimensional (3D) external geometry. However, mimicking the heterogeneous tissues that most organs and tissues are formed of is challenging. Although multiple-head 3D printing systems have been proposed for fabricating heterogeneous cell-laden hydrogel scaffolds, to date only the simple exterior form has been realized. Here we describe a computer-aided design and manufacturing (CAD/CAM) system for this application. We aim to develop an algorithm to enable easy, intuitive design and fabrication of a heterogeneous cell-laden hydrogel scaffolds with a free-form 3D geometry. The printing paths of the scaffold are automatically generated from the 3D CAD model, and the scaffold is then printed by dispensing four materials; i.e., a frame, two kinds of cell-laden hydrogel and a support. We demonstrated printing of heterogeneous tissue models formed of hydrogel scaffolds using this approach, including the outer ear, kidney and tooth tissue. These results indicate that this approach is particularly promising for tissue engineering and 3D printing applications to regenerate heterogeneous organs and tissues with tailored geometries to treat specific defects or injuries.

  5. Computer-aided multiple-head 3D printing system for printing of heterogeneous organ/tissue constructs

    Science.gov (United States)

    Jung, Jin Woo; Lee, Jung-Seob; Cho, Dong-Woo

    2016-01-01

    Recently, much attention has focused on replacement or/and enhancement of biological tissues via the use of cell-laden hydrogel scaffolds with an architecture that mimics the tissue matrix, and with the desired three-dimensional (3D) external geometry. However, mimicking the heterogeneous tissues that most organs and tissues are formed of is challenging. Although multiple-head 3D printing systems have been proposed for fabricating heterogeneous cell-laden hydrogel scaffolds, to date only the simple exterior form has been realized. Here we describe a computer-aided design and manufacturing (CAD/CAM) system for this application. We aim to develop an algorithm to enable easy, intuitive design and fabrication of a heterogeneous cell-laden hydrogel scaffolds with a free-form 3D geometry. The printing paths of the scaffold are automatically generated from the 3D CAD model, and the scaffold is then printed by dispensing four materials; i.e., a frame, two kinds of cell-laden hydrogel and a support. We demonstrated printing of heterogeneous tissue models formed of hydrogel scaffolds using this approach, including the outer ear, kidney and tooth tissue. These results indicate that this approach is particularly promising for tissue engineering and 3D printing applications to regenerate heterogeneous organs and tissues with tailored geometries to treat specific defects or injuries. PMID:26899876

  6. Investigations of the damage mechanisms during ultrashort pulse laser ablation of dental tissue

    Science.gov (United States)

    Domke, Matthias; Wick, Sebastian; Laible, Maike; Rapp, Stephan; Kuznetsova, Julia; Homann, Christian; Huber, Heinz P.; Sroka, Ronald

    2015-07-01

    Several investigations of dental tissue ablation with ultrashort pulsed lasers suggest that these lasers enable precise and selective material removal and reduce the formation of micro cracks and thermal effects, when compared to ns-pulses. In this study, two damage mechanisms are presented occurring during ablation of dentin using a laser emitting pulses of a duration of 380 fs at a wavelength of 1040 nm. First, it was found that nano cracks appear around the craters after single fs-pulse ablation. These cracks are directed to the crater and cross the dentinal tubules. Transient investigation of the single fs-pulse ablation process by pump-probe microscopy suggest that the driving mechanism could be a pressure wave that is released after stress confinement. Second, squared ablation holes were created by moving the laser focus at scan speeds between 0.5 mm/s and 2.0 m/s and fluences up to 14 J/cm2. It was found that deep cracks appear at the edges of the squared holes, if the scan speed is about 0.5 m/s. The fluence has only a minor impact on the crack formation. The crack propagation was investigated in the depth using x-ray micro tomography and optical coherence tomography. It was found that these cracks appear in the depth down to the dental pulp. These findings suggest that fast scanning of the laser beam is the key for damage free processing using ultrashort pulse lasers. Then, ablation rates of about 2.5 - 3.5 mm3/min/W can be achieved in dentine with pulse durations of 380 fs.

  7. Tissue inhibitor of metalloproteinase-3 (TIMP3) promotes endothelial apoptosis via a caspase-independent mechanism.

    Science.gov (United States)

    Qi, Jian Hua; Anand-Apte, Bela

    2015-04-01

    Tissue inhibitor of metalloproteinases-3 (TIMP3) is a tumor suppressor and a potent inhibitor of angiogenesis. TIMP3 exerts its anti-angiogenic effect via a direct interaction with vascular endothelial growth factor (VEGF) receptor-2 (KDR) and inhibition of proliferation, migration and tube formation of endothelial cells (ECs). TIMP3 has also been shown to induce apoptosis in some cancer cells and vascular smooth muscle cells via MMP inhibition and caspase-dependent mechanisms. In this study, we examined the molecular mechanisms of TIMP3-mediated apoptosis in endothelial cells. We have previously demonstrated that mice developed smaller tumors with decreased vascularity when injected with breast carcinoma cells overexpressing TIMP3, than with control breast carcinoma cells. TIMP3 overexpression resulted in increased apoptosis in human breast carcinoma (MDA-MB435) in vivo but not in vitro. However, TIMP3 could induce apoptosis in ECs in vitro. The apoptotic activity of TIMP3 in ECs appears to be independent of MMP inhibitory activity. Furthermore, the equivalent expression of functional TIMP3 promoted apoptosis and caspase activation in ECs expressing KDR (PAE/KDR), but not in ECs expressing PDGF beta-receptor (PAE/β-R). Surprisingly, the apoptotic activity of TIMP3 appears to be independent of caspases. TIMP3 inhibited matrix-induced focal adhesion kinase (FAK) tyrosine phosphorylation and association with paxillin and disrupted the incorporation of β3 integrin, FAK and paxillin into focal adhesion contacts on the matrix, which were not affected by caspase inhibitors. Thus, TIMP3 may induce apoptosis in ECs by triggering a caspase-independent cell death pathway and targeting a FAK-dependent survival pathway.

  8. [Tribological assessment of articular cartilage. A system for the analysis of the friction coefficient of cartilage, regenerates and tissue engineering constructs; initial results].

    Science.gov (United States)

    Schwarz, M L R; Schneider-Wald, B; Krase, A; Richter, W; Reisig, G; Kreinest, M; Heute, S; Pott, P P; Brade, J; Schütte, A

    2012-10-01

    Values for the friction coefficient of articular cartilage are given in ranges of percentage and lower and are calculated as a quotient of the friction force and the perpendicular loading force acting on it. Thus, a sophisticated system has to be provided for analysing the friction coefficient under different conditions in particular when cartilage should be coupled as friction partner. It is possible to deep-freeze articular cartilage before measuring the friction coefficient as the procedure has no influence on the results. The presented tribological system was able to distinguish between altered and native cartilage. Furthermore, tissue engineered constructs for cartilage repair were differentiated from native cartilage probes by their friction coefficient. In conclusion a tribological equipment is presented to analyze the friction coefficient of articular cartilage, in vivo generated cartilage regenerates and in vitro tissue engineered constructs regarding their biomechanical properties for quality assessment.

  9. Cross-linkable graphene oxide embedded nanocomposite hydrogel with enhanced mechanics and cytocompatibility for tissue engineering.

    Science.gov (United States)

    Liu, Xifeng; Miller, A Lee; Waletzki, Brian E; Lu, Lichun

    2017-12-27

    Graphene oxide (GO) is an attractive material that can be utilized to enhance the modulus and conductivities of substrates and hydrogels. To covalently cross-link graphene oxide sheets into hydrogels, abundant cross-linkable double bonds were introduced to synthesize the graphene-oxide-tris-acrylate sheet (GO-TrisA). Polyacrylamide (PAM) nanocomposite hydrogels were then fabricated with inherent covalently and permanently cross-linked GO-TrisA sheets. Results showed that the covalently cross-linked GO-TrisA/PAM nanocomposite hydrogel had enhanced mechanical strength, thermo stability compared with GO/PAM hydrogel maintained mainly by hydrogen bonding between PAM chains and GO sheets. In vitro cell study showed that the covalently cross-linked rGO-TrisA/PAM nanocomposite hydrogel had excellent cytocompatibility after in situ reduction. These results suggest that rGO-TrisA/PAM nanocomposite hydrogel holds great potential for tissue engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018. © 2017 Wiley Periodicals, Inc.

  10. Effects of alginate hydrogel cross-linking density on mechanical and biological behaviors for tissue engineering.

    Science.gov (United States)

    Jang, Jinah; Seol, Young-Joon; Kim, Hyeon Ji; Kundu, Joydip; Kim, Sung Won; Cho, Dong-Woo

    2014-09-01

    An effective cross-linking of alginate gel was made through reaction with calcium carbonate (CaCO3). We used human chondrocytes as a model cell to study the effects of cross-linking density. Three different pore size ranges of cross-linked alginate hydrogels were fabricated. The morphological, mechanical, and rheological properties of various alginate hydrogels were characterized and responses of biosynthesis of cells encapsulated in each gel to the variation in cross-linking density were investigated. Desired outer shape of structure was maintained when the alginate solution was cross-linked with the applied method. The properties of alginate hydrogel could be tailored through applying various concentrations of CaCO3. The rate of synthesized GAGs and collagens was significantly higher in human chondrocytes encapsulated in the smaller pore structure than that in the larger pore structure. The expression of chondrogenic markers, including collagen type II and aggrecan, was enhanced in the smaller pore structure. It was found that proper structural morphology is a critical factor to enhance the performance and tissue regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Mechanical properties of electrospun bilayer fibrous membranes as potential scaffolds for tissue engineering.

    Science.gov (United States)

    Pu, Juan; Komvopoulos, Kyriakos

    2014-06-01

    Bilayer fibrous membranes of poly(l-lactic acid) (PLLA) were fabricated by electrospinning, using a parallel-disk mandrel configuration that resulted in the sequential deposition of a layer with fibers aligned across the two parallel disks and a layer with randomly oriented fibers, both layers deposited in a single process step. Membrane structure and fiber alignment were characterized by scanning electron microscopy and two-dimensional fast Fourier transform. Because of the intricacies of the generated electric field, bilayer membranes exhibited higher porosity than single-layer membranes consisting of randomly oriented fibers fabricated with a solid-drum collector. However, despite their higher porosity, bilayer membranes demonstrated generally higher elastic modulus, yield strength and toughness than single-layer membranes with random fibers. Bilayer membrane deformation at relatively high strain rates comprised multiple abrupt microfracture events characterized by discontinuous fiber breakage. Bilayer membrane elongation yielded excessive necking of the layer with random fibers and remarkable fiber stretching (on the order of 400%) in the layer with fibers aligned in the stress direction. In addition, fibers in both layers exhibited multiple localized necking, attributed to the nonuniform distribution of crystalline phases in the fibrillar structure. The high membrane porosity, good mechanical properties, and good biocompatibility and biodegradability of PLLA (demonstrated in previous studies) make the present bilayer membranes good scaffold candidates for a wide range of tissue engineering applications. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  12. A study on improving mechanical properties of porous HA tissue engineering scaffolds by hot isostatic pressing

    International Nuclear Information System (INIS)

    Zhao Jing; Xiao Suguang; Lu Xiong; Wang Jianxin; Weng Jie

    2006-01-01

    Various interconnected porous hydroxyapatite (HA) ceramic scaffolds are universally used to induct the tissue growth for bone repair and replacement, and serve to support the adhesion, transfer, proliferation and differentiation of cells. Impregnation of polyurethane sponges with a ceramic slurry is adopted to produce highly porous HA ceramic scaffolds with a 3D interconnected structure. However, high porosity always accompanies a decrease in the strength of the HA ceramic scaffolds. Therefore, it is significant to improve the strength of the HA ceramic scaffolds with highly interconnected porosity so that they are more suitable in clinical applications. In this work, highly porous HA ceramic scaffolds are first produced by the polymer impregnation approach, and subsequently further sintered by hot isostatic pressing (HIP). The phase composition, macro- and micro-porous structure, sintering and mechanical properties of the porous HA scaffolds are investigated by x-ray diffraction (XRD), scanning electron microscopy (SEM), nanoindentation analysis and compressive test. The experimental results show that the nanohardness and compressive strength of HIP-sintered porous HA ceramics are higher than those of commonly sintered HA scaffolds. The HIP technique can effectively improve the sintering property and densification of porous HA ceramic scaffolds, so inducing an increase in the compression strength

  13. Interactive mechanism of working environments and construction behaviors with cognitive work analysis: an elevator installation case study.

    Science.gov (United States)

    Wang, Yanqing; Chong, Heap-Yih; Liao, Pin-Chao; Ren, Hantao

    2017-09-25

    Unsafe behavior is a leading factor in accidents, and the working environment significantly affects behaviors. However, few studies have focused on detailed mechanisms for addressing unsafe behaviors resulting from environmental constraints. This study aims to delineate these mechanisms using cognitive work analysis (CWA) for an elevator installation case study. Elevator installation was selected for study because it involves operations at heights: falls from heights remain a major cause of construction worker mortality. This study adopts a mixed research approach based on three research methodology stages. This research deconstructs the details of the working environment, the workers' decision-making processes, the strategies chosen given environmental conditions and the conceptual model for workers' behaviors, which jointly depict environment-behavior mechanisms at length. By applying CWA to the construction industry, environmental constraints can easily be identified, and targeted engineering suggestions can be generated.

  14. Characterization of tissue-equivalent materials for use in construction of physical phantoms; Caracterizacao de materiais tecido-equivalentes para uso em construcao de fantomas fisicos

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Edvan V. de, E-mail: edvanmsn@hotmail.com [Instituto Federal de Educacao, Ciencia e Tecnologia de Pernambuco (IFFPE), Recife, PE (Brazil); Oliveira, Alex C.H. de, E-mail: oliveira_ach@yahoo.com [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Vieira, Jose W., E-mail: jose.wilson59@uol.com.br [Escola Politecnica de Pernambuco (UPE), Recife, PE (Brazil); Lima, Fernando R.A., E-mail: falima@cenen.gov.br [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2013-07-01

    Phantoms are physical or computational models used to simulate the transport of ionizing radiation, their interactions with human body tissues and evaluate the deposition of energy. Depending on the application, you can build phantoms of various types and features. The physical phantoms are made of materials with behavior similar to human tissues exposed to ionizing radiation, the so-called tissue-equivalent materials. The characterization of various tissue-equivalent materials is important for the choice of materials to be used is appropriate, seeking a better cost-benefit ratio. The main objective of this work is to produce tables containing the main characteristics of tissue-equivalent materials. These tables were produced in Microsoft Office Excel. Among the main features of tissue-equivalent materials that were added to the tables, are density, chemical composition, physical state, chemical stability and solubility. The main importance of this work is to contribute to the construction of high-quality physical phantoms and avoid the waste of materials.

  15. Mechanical and biological properties of the micro-/nano-grain functionally graded hydroxyapatite bioceramics for bone tissue engineering.

    Science.gov (United States)

    Zhou, Changchun; Deng, Congying; Chen, Xuening; Zhao, Xiufen; Chen, Ying; Fan, Yujiang; Zhang, Xingdong

    2015-08-01

    Functionally graded materials (FGM) open the promising approach for bone tissue repair. In this study, a novel functionally graded hydroxyapatite (HA) bioceramic with micrograin and nanograin structure was fabricated. Its mechanical properties were tailored by composition of micrograin and nanograin. The dynamic mechanical analysis (DMA) indicated that the graded HA ceramics had similar mechanical property compared to natural bones. Their cytocompatibility was evaluated via fluorescent microscopy and MTT colorimetric assay. The viability and proliferation of rabbit bone marrow mesenchymal stem cells (BMSCs) on ceramics indicated that this functionally graded HA ceramic had better cytocompatibility than conventional HA ceramic. This study demonstrated that functionally graded HA ceramics create suitable structures to satisfy both the mechanical and biological requirements of bone tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Mechanical, Biological and Electrochemical Investigations of Advanced Micro/Nano Materials for Tissue Engineering and Energy Storage

    Science.gov (United States)

    Pu, Juan

    Various micro/nano materials have been extensively studied for applications in tissue engineering and energy storage. Tissue engineering seeks to repair or replace damaged tissue by integrating approaches from cellular/molecular biology and material chemistry/engineering. A major challenge is the consistent design of three-dimensional (3D) scaffolds that mimic the structure and biological functions of extracellular matrix (ECM), guide cell migration, provide mechanical support, and regulate cell activity. Electrospun micro/nanofibers have been investigated as promising tissue engineering scaffolds because they resemble native ECM and possess tunable surface morphologies. Supercapacitors, one of the energy storage devices, bridge the performance gap between rechargeable batteries and conventional capacitors. Active electrode materials of supercapacitors must possess high specific surface area, high conductivity, and good electrochemical properties. Carbon-based micro/nano-particles, such as graphene, activated carbon (AC), and carbon nanotubes, are commonly used as active electrode materials for storing charge in supercapacitors by the electrical double layer mechanism due to their high specific surface area and excellent conductivity. In this thesis, the mechanical properties of electrospun bilayer microfibrous membranes were investigated for potential applications in tissue engineering. Bilayer microfibrous membranes of poly(l-lactic acid) (PLLA) were fabricated by electrospinning using a parallel-disk mandrel configuration, which resulted in the sequential deposition of a layer with aligned fibers (AFL) across the two parallel disks and a layer with random fibers (RFL), both deposited by a single process step. The membrane structure and fiber alignment were characterized by scanning electron microscopy and two-dimensional fast Fourier transform. Because of the intricacies of the generated electric field, the bilayer membranes exhibited higher porosity than the

  17. Construction of high-density tissue microarrays at low cost by using self-made manual microarray kits and recipient paraffin blocks.

    Science.gov (United States)

    Choi, Chang Hwan; Kim, Kyu Ho; Song, Ju Young; Choi, Suk Jin; Kim, Lucia; Park, In Suh; Han, Jee Young; Kim, Joon Mee; Chu, Young Chae

    2012-12-01

    Advances of tissue microarray (TMA) technology have enabled simultaneous in situ analysis of biomarker expression in a large number of archived pathology specimens. However, the relatively high cost of TMA construction may hamper many researchers from using this essential tool of modern pathology research. We discuss methods for making TMA kits and recipient blocks for manual construction of high-density TMAs at low cost. Ordinary cannula piercing needles, hypodermic needles, bone marrow biopsy needles, metallic ink cartridges of ballpoint pens, and disposable skin biopsy punches were used to construct self-made manual TMA kits. The recipient blocks were manufactured by boring holes in the conventional bare paraffin blocks. A mini electric hand drill and a microcompound table assembled on a drill stand were used to maximize the capacity of the recipient blocks. By using TMA kits made from cannula piercing needles (16- and 18-gauge), it was possible to construct TMAs with 1 mm×140 cores, 0.6 mm×320 cores, 2 mm×70 cores, 3 mm×35 cores, and 5 mm×12 cores. The capacity of the recipient blocks could be dramatically increased by drilling holes. Construction of TMAs using self-made TMA kits is an inexpensive alternative to construction of TMAs using commercial devices.

  18. Application of an object-oriented programming paradigm in three-dimensional computer modeling of mechanically active gastrointestinal tissues.

    Science.gov (United States)

    Rashev, P Z; Mintchev, M P; Bowes, K L

    2000-09-01

    The aim of this study was to develop a novel three-dimensional (3-D) object-oriented modeling approach incorporating knowledge of the anatomy, electrophysiology, and mechanics of externally stimulated excitable gastrointestinal (GI) tissues and emphasizing the "stimulus-response" principle of extracting the modeling parameters. The modeling method used clusters of class hierarchies representing GI tissues from three perspectives: 1) anatomical; 2) electrophysiological; and 3) mechanical. We elaborated on the first four phases of the object-oriented system development life-cycle: 1) analysis; 2) design; 3) implementation; and 4) testing. Generalized cylinders were used for the implementation of 3-D tissue objects modeling the cecum, the descending colon, and the colonic circular smooth muscle tissue. The model was tested using external neural electrical tissue excitation of the descending colon with virtual implanted electrodes and the stimulating current density distributions over the modeled surfaces were calculated. Finally, the tissue deformations invoked by electrical stimulation were estimated and represented by a mesh-surface visualization technique.

  19. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim

  20. A new technique in constructing closed-form solutions for nonlinear PDEs appearing in fluid mechanics and gas dynamics

    Directory of Open Access Journals (Sweden)

    Panayotounakos D. E.

    1996-01-01

    Full Text Available We develop a new unique technique in constructing closed-form solutions for several nonlinear partial differential systems appearing in fluid mechanics and gas dynamics. The obtained solutions include fewer arbitrary functions than needed for general solutions, fact that permits us to specify them according to the initial state, or the geometry, of each specific problem under consideration. In order to apply the before mentioned technique we construct closed-form solutions concerning the gas-dynamic equations with constant pressure, the dynamic equations of an ideal gas in isentropic flow, and the two-dimensional incompressible boundary layer flow.

  1. Three-dimensional radiofrequency tissue tightening: a proposed mechanism and applications for body contouring.

    Science.gov (United States)

    Paul, Malcolm; Blugerman, G; Kreindel, M; Mulholland, R S

    2011-02-01

    The use of radiofrequency energy to produce collagen matrix contraction is presented. Controlling the depth of energy delivery, the power applied, the target skin temperature, and the duration of application of energy at various soft tissue levels produces soft tissue contraction, which is measurable. This technology allows precise soft tissue modeling at multiple levels to enhance the result achieved over traditional suction-assisted lipectomy as well as other forms of energy such as ultrasonic and laser-generated lipolysis.

  2. Biaxial mechanics and inter-lamellar shearing of stem-cell seeded electrospun angle-ply laminates for annulus fibrosus tissue engineering.

    Science.gov (United States)

    Driscoll, Tristan P; Nakasone, Ryan H; Szczesny, Spencer E; Elliott, Dawn M; Mauck, Robert L

    2013-06-01

    The annulus fibrosus (AF) of the intervertebral disk plays a critical role in vertebral load transmission that is heavily dependent on the microscale structure and composition of the tissue. With degeneration, both structure and composition are compromised, resulting in a loss of AF mechanical function. Numerous tissue engineering strategies have addressed the issue of AF degeneration, but few have focused on recapitulation of AF microstructure and function. One approach that allows for generation of engineered AF with appropriate (+/-)30° lamellar microstructure is the use of aligned electrospun scaffolds seeded with mesenchymal stem cells (MSCs) and assembled into angle-ply laminates (APL). Previous work indicates that opposing lamellar orientation is necessary for development of near native uniaxial tensile properties. However, most native AF tensile loads are applied biaxially, as the disk is subjected to multi-axial loads and is constrained by its attachments to the vertebral bodies. Thus, the objective of this study was to evaluate the biaxial mechanical response of engineered AF bilayers, and to determine the importance of opposing lamellar structure under this loading regime. Opposing bilayers, which replicate native AF structure, showed a significantly higher modulus in both testing directions compared to parallel bilayers, and reached ∼60% of native AF biaxial properties. Associated with this increase in biaxial properties, significantly less shear, and significantly higher stretch in the fiber direction, was observed. These results provide additional insight into native tissue structure-function relationships, as well as new benchmarks for engineering functional AF tissue constructs. Copyright © 2013 Orthopaedic Research Society.

  3. In vitro tendon tissue development from human fibroblasts demonstrates collagen fibril diameter growth associated with a rise in mechanical strength

    DEFF Research Database (Denmark)

    Herchenhan, Andreas; Bayer, Monika L; Svensson, René B

    2013-01-01

    Collagen-rich tendons and ligaments are important for joint stability and force transmission, but the capacity to form new tendon is poorly understood. In the present study, we investigated mechanical strength, fibril size, and structure during development of tendon-like tissue from adult human...

  4. Hydrogel fibers for ACL prosthesis: design and mechanical evaluation of PVA and PVA/UHMWPE fiber constructs.

    Science.gov (United States)

    Bach, Jason S; Detrez, Fabrice; Cherkaoui, Mohammed; Cantournet, Sabine; Ku, David N; Corté, Laurent

    2013-05-31

    Prosthetic devices for anterior cruciate ligament (ACL) reconstruction have been unsuccessful due to mechanical failure or chronic inflammation. Polymer hydrogels combine biocompatibility and unique low friction properties; however, their prior use for ligament reconstruction has been restricted to coatings due to insufficient tensile mechanics. Here, we investigate new constructs of polyvinyl alcohol (PVA) hydrogel fibers. In water, these fibers swell to an equilibrium water content of 50% by weight, retaining a tensile modulus greater than 40 MPa along the fiber axis at low strain. Rope constructs were assembled for ACL replacement and mechanical properties were compared with data from the literature. Pure PVA hydrogel constructs closely reproduce the non-linear tensile stiffness of the native ACL with an ultimate strength of about 2000 N. An additional safety factor in tensile strength was achieved with composite braids by adding ultrahigh molecular weight polyethylene (UHMWPE) fibers around a core of PVA cords. Composition and braiding angle are adjusted to produce a non-linear tensile behavior within the range of the native ligament that can be predicted by a simple rope model. This design was found to sustain over one million cycles between 50 and 450 N with limited damage and less than 20% creep. The promising mechanical performances of these systems provide justification for more extensive in vivo evaluation. Copyright © 2013. Published by Elsevier Ltd.

  5. Mechanical pain sensitivity of deep tissues in children - possible development of myofascial trigger points in children

    Directory of Open Access Journals (Sweden)

    Han Ting-I

    2012-02-01

    Full Text Available Abstract Background It is still unclear when latent myofascial trigger points (MTrPs develop during early life. This study is designed to investigate the mechanical pain sensitivity of deep tissues in children in order to see the possible timing of the development of latent MTrPs and attachment trigger points (A-TrPs in school children. Methods Five hundreds and five healthy school children (age 4- 11 years were investigated. A pressure algometer was used to measure the pressure pain threshold (PPT at three different sites in the brachioradialis muscle: the lateral epicondyle at elbow (site A, assumed to be the A-TrP site, the mid-point of the muscle belly (site B, assumed to be the MTrP site, and the muscle-tendon junction as a control site (site C. Results The results showed that, for all children in this study, the mean PPT values was significantly lower (p p Conclusions It is concluded that a child had increased sensitivity at the tendon attachment site and the muscle belly (endplate zone after age of 4 years. Therefore, it is likely that a child may develop an A-Trp and a latent MTrP at the brachioradialis muscle after the age of 4 years. The changes in sensitivity, or the development for these trigger points, may not be related to the activity level of children aged 7-11 years. Further investigation is still required to indentify the exact timing of the initial occurrence of a-Trps and latent MTrPs.

  6. Molecular mechanism of tissue factor-mediated acceleration of factor VIIa activity.

    Science.gov (United States)

    Higashi, S; Matsumoto, N; Iwanaga, S

    1996-10-25

    The mechanism of the acceleration of the catalytic activity of factor VIIa (VIIa) in the presence of tissue factor (TF) was investigated. To explore the VIIa's site(s) that correlates with TF-mediated acceleration, zymogen VII, VIIa, and active site-modified VIIa were prepared, and dissociation constants (Kd) for their bindings to TF or soluble TF in solution were determined. We found that conversion of zymogen VII to VIIa led to an increase in affinity (DeltaDeltaG = 4.3-4.4 kJ/mol) for TFs. Dansyl-Glu-Gly-Arg chloromethyl ketone (DNS-EGRck) treatment of VIIa led to a further increase in the affinity (DeltaDeltaG = 7.3-12 kJ/mol). Neither removal of the Gla domain from VIIa nor truncation of the COOH-terminal membrane and cytoplasmic regions of TF affected the affinity enhanced after DNS-EGRck treatment of VIIa. Treatment of VIIa with (p-amidinophenyl)methanesulfonyl fluoride also enhanced its affinity for soluble TF, whereas treatment with 4-(2-aminoethyl)benzenesulfonyl fluoride, phenylmethylsulfonyl fluoride, or diisopropyl fluorophosphate had a slight effect on the affinity. On the other hand, DNS-EGRck and (p-amidinophenyl)methanesulfonyl fluoride treatments, but not diisopropyl fluorophosphate treatment, of VIIa led to protection of its alpha-amino group of Ile-153 from carbamylation. Protection of the alpha-amino group was consistent with formation of a critical salt bridge between Ile-153 and Asp-343 in the protease domain of VIIa. Therefore, TF may preferentially bind to the active conformational state of VIIa. When one assumes that free VIIa exists in equilibrium between minor active and dominant zymogen-like inactive conformational states, preferential binding of TF to the active state leads to a shift in equilibrium. We speculate that TF traps the active conformational state of VIIa and converts its zymogen-like state into an active state, thereby accelerating the VIIa activity.

  7. A CAREM fuel assembly prototype construction in order to verify its mechanical design using hydrodynamic testing

    International Nuclear Information System (INIS)

    Aparicio, Gaspar; Di Marco, Agustin; Falcone, Jose M.; Giorgis, Miguel A.; Mathot, Sergio R.; Migliori, Julio; Orlando, Oscar S.; Restelli, Miguel A.; Ruggirello, Gabriel; Sapia, Gustavo C.; Zinzallari, Fausto; Bianchi, Daniel R.; Volpi, Ricardo M.

    2000-01-01

    The scope of this paper is to describe the activities of several Groups from three Atomic Centers (C. A. Bariloche, C. A. Ezeiza and C. A. Constituyentes), involved in the manufacturing of a CAREM fuel assembly prototype. The Design Group (UAIN-CAB) carried out the fuel assembly engineering. Cladding components were constructed by the Special Alloys Pilot Factory (UAMCN-CAE). Engineering Group (UACN-CAC) manufactured the parts to be processed, resorting to qualified suppliers. Elastic spacers were completely designed and constructed by this Group, and fuel rods, control rods, guide tubes and spacers were also welded here. Research Reactors Fuels Group (UACN-CAC) carried out the dimensional control of the elaborated parts, while Postirradiation Testing Group (UACN-CAC) performed the assembling of the fuel element. This paper also refers to the design and development of special equipment and devices, all of them required for the prototype construction. (author)

  8. Mechanisms of foot-and-mouth disease virus tropism inferred from differential tissue gene expression

    Science.gov (United States)

    Foot-and-Mouth Disease virus (FMDV) has a characteristic tropism in terms of primary, secondary, and persistent infection and vesicular lesion sites. The virus targets specific tissues for primary replication. From these tissues, the virus spreads via the blood stream to a few preferred secondary in...

  9. Core-firm Based View on the Mechanism of Constructing a Corporate Innovation Ecosystem

    DEFF Research Database (Denmark)

    Jiang, Shimei; Wang, Ziyuan; Hu, Yimei

    2016-01-01

    constructing a corporate innovation ecosystem through building up an innovation platform that include multi-level collaborative relationships based on different technologies; while at the same time integrating non-technological issues such as strategy, culture, management, organization, institution and market......The fierce transformation of the competitive status of business world in the 21st century has urged the innovation activities turned from mechanistic and deterministic to ecological and organic. The study firstly defines the concept of core firm based on reviewing existing corporate innovation....... This research complements and extends literature on corporate innovation ecosystem, and provides implications to innovative companies on constructing a core firm based innovation ecosystem....

  10. Biophysical and biochemical models of mechanisms of cellular development via the cellular cycle in normal tissue, cancerous tissue, and inflammatory processes.

    Science.gov (United States)

    Ponizovskiy, M R

    2013-01-01

    The significant separate biochemical discoveries of pro- and anti-apoptotic -autophagy, and -proliferative processes in normal and pathology cells were learned in detail from the point of view of biophysics, physical chemistry, and thermodynamics, which made possible the proposal that a common mechanism relates to all of these processes: intracellular balances in catabolic and anabolic processes interconnect with extracellular balances, promoting and maintaining the stability of internal medium and internal energy of cells as well as normal cell development. Nevertheless, violations to these interconnections of intracellular and extracellular balances promote pathologic processes. The study of cellular cycle mechanisms in normal cells explained the mechanisms of the maintenance of stability of the internal medium and internal energy of cells as a component of the overall stability of an organism. It explained the development of the cellular cycle as the oscillating changes in the flow of energy and substances. In addition, violations to mechanisms of the maintenance of stability of the cellular internal medium and internal energy in cancer tissue were elucidated and compared with violations of these mechanisms in inflammatory processes. All of this eliminated a lot of doubts and queries that were expressed by the authors of some experiments.

  11. Comparison of the mechanical characteristics of polymerized caprolactam and monofilament nylon loops constructed in parallel strands or as braided ropes versus cranial cruciate ligaments of cattle.

    Science.gov (United States)

    Niehaus, Andrew J; Anderson, David E; Johnson, Jed K; Lannutti, John J

    2013-03-01

    To compare the mechanical characteristics of polymerized caprolactam and monofilament nylon loops with those of the cranial cruciate ligament (CCL) in cattle. 6 femorotibial joints harvested from 3 cows and suture constructs made from No. 8 polymerized caprolactam, 80-lb test monofilament nylon fishing line, and 450-lb test monofilament nylon fishing line. Joints were cleared of soft tissue structures except the CCL, connected to a load frame, and loaded to failure while measuring force and elongation. Synthetic constructs tested in a similar manner included single-stranded and 3-stranded No. 8 polymerized caprolactam, 3- and 6-stranded 80-lb test monofilament nylon fishing line, and 3- and 6-stranded 450-lb test monofilament nylon fishing line. The CCL ruptured at a mean ± SD force of 4,541 ± 1,417 N with an elongation of 2.0 ± 0.3 cm. The tensile strength of 3-stranded 450-lb test monofilament nylon fishing line was similar to that of the CCL, rupturing at loads of 5,310 ± 369 N (braided strands) and 6,260 ± 239 N (parallel strands). Elongation was greater for braided constructs. The 3-stranded cords of 450-lb test monofilament nylon fishing line most closely approximated the strength of the CCL. Marked increases in elongation occur when large-sized materials are constructed in braided configurations, and this elongation would likely not provide stability in CCL-deficient stifle joints. Additional studies are needed to determine whether any of these materials are suitable CCL replacements in cattle.

  12. Association between traumatic bone marrow abnormalities of the knee, the trauma mechanism and associated soft-tissue knee injuries

    Energy Technology Data Exchange (ETDEWEB)

    Berger, Nicole [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); University of Zurich, Department of Forensic Medicine and Radiology, Institute of Forensic Medicine, Zurich (Switzerland); Andreisek, Gustav; Karer, Anissja T.; Manoliu, Andrei; Ulbrich, Erika J. [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Bouaicha, Samy [University Hospital Zurich, Department of Trauma Surgery, Zurich (Switzerland); Naraghi, Ali [University of Toronto, Department of Medical Imaging, Mount Sinai Hospital and the University Health Network, Toronto, ON (Canada); Seifert, Burkhardt [University of Zurich, Epidemiology, Biostatistics and Prevention Institute, Department of Biostatistics, Zurich (Switzerland)

    2017-01-15

    To determine the association between traumatic bone marrow abnormalities, the knee injury mechanism, and associated soft tissue injuries in a larger cohort than those in the published literature. Retrospective study including 220 patients with traumatic knee injuries. Knee MRIs were evaluated for trauma mechanism, soft tissue injury, and the location of bone marrow abnormalities. The locations of the abnormalities were correlated with trauma mechanisms and soft tissue injuries using the chi-square test with Bonferroni correction. One hundred and forty-four valgus injuries, 39 pivot shift injuries, 25 lateral patellar dislocations, 8 hyperextensions, and 4 dashboard injuries were included. Valgus and pivot shift injuries showed traumatic bone marrow abnormalities in the posterolateral regions of the tibia. Abnormalities after patellar dislocation were found in the anterolateral and centrolateral femur and patella. Hyperextension injuries were associated with abnormalities in almost all regions, and dashboard injuries were associated with changes in the anterior regions of the tibia and femur. Our study provides evidence of associations between traumatic bone marrow abnormality patterns and different trauma mechanisms in acute knee injury, and reveals some overlap, especially of the two most common trauma mechanisms (valgus and pivot shift), in a large patient cohort. (orig.)

  13. Mechanical properties and cellular response of novel electrospun nanofibers for ligament tissue engineering: Effects of orientation and geometry.

    Science.gov (United States)

    Pauly, Hannah M; Kelly, Daniel J; Popat, Ketul C; Trujillo, Nathan A; Dunne, Nicholas J; McCarthy, Helen O; Haut Donahue, Tammy L

    2016-08-01

    Electrospun nanofibers are a promising material for ligamentous tissue engineering, however weak mechanical properties of fibers to date have limited their clinical usage. The goal of this work was to modify electrospun nanofibers to create a robust structure that mimics the complex hierarchy of native tendons and ligaments. The scaffolds that were fabricated in this study consisted of either random or aligned nanofibers in flat sheets or rolled nanofiber bundles that mimic the size scale of fascicle units in primarily tensile load bearing soft musculoskeletal tissues. Altering nanofiber orientation and geometry significantly affected mechanical properties; most notably aligned nanofiber sheets had the greatest modulus; 125% higher than that of random nanofiber sheets; and 45% higher than aligned nanofiber bundles. Modifying aligned nanofiber sheets to form aligned nanofiber bundles also resulted in approximately 107% higher yield stresses and 140% higher yield strains. The mechanical properties of aligned nanofiber bundles were in the range of the mechanical properties of the native ACL: modulus=158±32MPa, yield stress=57±23MPa and yield strain=0.38±0.08. Adipose derived stem cells cultured on all surfaces remained viable and proliferated extensively over a 7 day culture period and cells elongated on nanofiber bundles. The results of the study suggest that aligned nanofiber bundles may be useful for ligament and tendon tissue engineering based on their mechanical properties and ability to support cell adhesion, proliferation, and elongation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Association between traumatic bone marrow abnormalities of the knee, the trauma mechanism and associated soft-tissue knee injuries

    International Nuclear Information System (INIS)

    Berger, Nicole; Andreisek, Gustav; Karer, Anissja T.; Manoliu, Andrei; Ulbrich, Erika J.; Bouaicha, Samy; Naraghi, Ali; Seifert, Burkhardt

    2017-01-01

    To determine the association between traumatic bone marrow abnormalities, the knee injury mechanism, and associated soft tissue injuries in a larger cohort than those in the published literature. Retrospective study including 220 patients with traumatic knee injuries. Knee MRIs were evaluated for trauma mechanism, soft tissue injury, and the location of bone marrow abnormalities. The locations of the abnormalities were correlated with trauma mechanisms and soft tissue injuries using the chi-square test with Bonferroni correction. One hundred and forty-four valgus injuries, 39 pivot shift injuries, 25 lateral patellar dislocations, 8 hyperextensions, and 4 dashboard injuries were included. Valgus and pivot shift injuries showed traumatic bone marrow abnormalities in the posterolateral regions of the tibia. Abnormalities after patellar dislocation were found in the anterolateral and centrolateral femur and patella. Hyperextension injuries were associated with abnormalities in almost all regions, and dashboard injuries were associated with changes in the anterior regions of the tibia and femur. Our study provides evidence of associations between traumatic bone marrow abnormality patterns and different trauma mechanisms in acute knee injury, and reveals some overlap, especially of the two most common trauma mechanisms (valgus and pivot shift), in a large patient cohort. (orig.)

  15. Fact versus artifact: Avoiding erroneous estimates of sulfated glycosaminoglycan content using the dimethylmethylene blue colorimetric assay for tissue-engineered constructs

    Directory of Open Access Journals (Sweden)

    CH Zheng

    2015-04-01

    Full Text Available The 1,9-dimethylmethylene blue (DMMB assay is widely used to quantify sulfated glycosaminoglycan (sGAG contents of engineered tissues, culture media, tissue samples and bodily fluids, but the assay is subject to interference from polyanions such as hyaluronic acid (HA, DNA and RNA. We examined whether specific combinations of dye pH and absorbance wavelength could minimize non-sGAG artifacts without compromising DMMB assay sensitivity. HA and DNA solutions generated substantial signal at pH 3 but not at pH 1.5. Reducing dye pH did not significantly alter sGAG measurements for normal cartilage and meniscus tissues, but eliminated anomalously high apparent sGAG contents for enzymatically isolated chondrocytes, adipose-derived stem cell (ADSC-agarose constructs and ADSC pellets. In a cartilage tissue-engineering case study, pH 3 dye indicated high apparent sGAG readings throughout culture in both basal and chondrogenic media, with a marked decline between day 14 and 21 for chondrogenic constructs. The pH 1.5 dye, however, indicated minimal sGAG accumulation in basal medium and stable sGAG content throughout culture in chondrogenic medium. As it is often difficult to know a priori whether all groups in a study will have sGAG contents high enough to overwhelm artifacts, we recommend modifying the standard DMMB assay to reduce the risk of spurious findings in tissue engineering and clinical research. Specifically, we recommend shifting to a pH 1.5 DMMB dye and basing quantification on the absorbance difference between 525 nm (µ peak and 595 nm (β peak to compensate for the moderate loss of sensitivity associated with reducing the dye pH.

  16. Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics.

    Directory of Open Access Journals (Sweden)

    Maryna Perepelyuk

    Full Text Available Tissues including liver stiffen and acquire more extracellular matrix with fibrosis. The relationship between matrix content and stiffness, however, is non-linear, and stiffness is only one component of tissue mechanics. The mechanical response of tissues such as liver to physiological stresses is not well described, and models of tissue mechanics are limited. To better understand the mechanics of the normal and fibrotic rat liver, we carried out a series of studies using parallel plate rheometry, measuring the response to compressive, extensional, and shear strains. We found that the shear storage and loss moduli G' and G" and the apparent Young's moduli measured by uniaxial strain orthogonal to the shear direction increased markedly with both progressive fibrosis and increasing compression, that livers shear strain softened, and that significant increases in shear modulus with compressional stress occurred within a range consistent with increased sinusoidal pressures in liver disease. Proteoglycan content and integrin-matrix interactions were significant determinants of liver mechanics, particularly in compression. We propose a new non-linear constitutive model of the liver. A key feature of this model is that, while it assumes overall liver incompressibility, it takes into account water flow and solid phase compressibility. In sum, we report a detailed study of non-linear liver mechanics under physiological strains in the normal state, early fibrosis, and late fibrosis. We propose a constitutive model that captures compression stiffening, tension softening, and shear softening, and can be understood in terms of the cellular and matrix components of the liver.

  17. Inhibition of COX1/2 alters the host response and reduces ECM scaffold mediated constructive tissue remodeling in a rodent model of skeletal muscle injury.

    Science.gov (United States)

    Dearth, Christopher L; Slivka, Peter F; Stewart, Scott A; Keane, Timothy J; Tay, Justin K; Londono, Ricardo; Goh, Qingnian; Pizza, Francis X; Badylak, Stephen F

    2016-02-01

    Extracellular matrix (ECM) has been used as a biologic scaffold material to both reinforce the surgical repair of soft tissue and serve as an inductive template to promote a constructive tissue remodeling response. Success of such an approach is dependent on macrophage-mediated degradation and remodeling of the biologic scaffold. Macrophage phenotype during these processes is a predictive factor of the eventual remodeling outcome. ECM scaffolds have been shown to promote an anti-inflammatory or M2-like macrophage phenotype in vitro that includes secretion of downstream products of cycolooxygenases 1 and 2 (COX1/2). The present study investigated the effect of a common COX1/2 inhibitor (Aspirin) on macrophage phenotype and tissue remodeling in a rodent model of ECM scaffold treated skeletal muscle injury. Inhibition of COX1/2 reduced the constructive remodeling response by hindering myogenesis and collagen deposition in the defect area. The inhibited response was correlated with a reduction in M2-like macrophages in the defect area. The effects of Aspirin on macrophage phenotype were corroborated using an established in vitro macrophage model which showed a reduction in both ECM induced prostaglandin secretion and expression of a marker of M2-like macrophages (CD206). These results raise questions regarding the common peri-surgical administration of COX1/2 inhibitors when biologic scaffold materials are used to facilitate muscle repair/regeneration. COX1/2 inhibitors such as nonsteroidal anti-inflammatory drugs (NSAIDs) are routinely administered post-surgically for analgesic purposes. While COX1/2 inhibitors are important in pain management, they have also been shown to delay or diminish the healing process, which calls to question their clinical use for treating musculotendinous injuries. The present study aimed to investigate the influence of a common NSAID, Aspirin, on the constructive remodeling response mediated by an ECM scaffold (UBM) in a rat skeletal

  18. Induction of hyperresponsiveness in human airway tissue by neutrophils--mechanism of action.

    Science.gov (United States)

    Anticevich, S Z; Hughes, J M; Black, J L; Armour, C L

    1996-05-01

    The two main features of asthma are bronchial hyperresponsiveness and inflammation. The inflammatory response in asthma consists of infiltration and activation of a variety of inflammatory cells including neutrophils. Our previous studies have shown that stimulated neutrophil supernatants cause hyperresponsiveness of human bronchial tissue in vitro. To investigate the effect of the sensitization status of the tissue and the albumin concentration used to prepare supernatants on the response of human bronchial tissue to stimulated neutrophil supernatants. Neutrophil supernatants were prepared from human isolated blood in the presence of varying concentrations of albumin (0%, 0.1% and 4%). Neutrophil supernatants were added to sensitized and non-sensitized human isolated bronchial tissue which was stimulated with electrical field stimulation (EFS) (20 s every 4 min). Receptor antagonists specific for the prostaglandin and thromboxane (10(-7) M GR32191), platelet activating factor (10(-6) M WEB 2086), leukotriene D4 (10(-6) M MK-679) and neurokinin A (10(-7) M SR48968) receptors were used to identify neutrophil products responsible for the effects observed in the bronchial tissue. In non-sensitized human bronchial tissue, stimulated neutrophil supernatants induced a direct contraction in the presence of 0% and 0.1% but not 4% albumin. This contraction was due to leukotriene D4 as MK-679 completely inhibited the contraction. In contrast, stimulated neutrophil supernatants increased responsiveness of sensitized human bronchial tissue to EFS. The increased responsiveness was observed only in the presence of 0.1% albumin, with the site of modulation likely to be prejunctional on the parasympathetic nerve. The increased responsiveness was not inhibited by any of the antagonists tested. Sensitization status of the tissue and albumin concentration effect the responsiveness of human bronchial tissue to stimulated neutrophil supernatant. Our results suggest a possible role for

  19. Traits, properties, and performance: how woody plants combine hydraulic and mechanical functions in a cell, tissue, or whole plant.

    Science.gov (United States)

    Lachenbruch, Barbara; McCulloh, Katherine A

    2014-12-01

    This review presents a framework for evaluating how cells, tissues, organs, and whole plants perform both hydraulic and mechanical functions. The morphological alterations that affect dual functionality are varied: individual cells can have altered morphology; tissues can have altered partitioning to functions or altered cell alignment; and organs and whole plants can differ in their allocation to different tissues, or in the geometric distribution of the tissues they have. A hierarchical model emphasizes that morphological traits influence the hydraulic or mechanical properties; the properties, combined with the plant unit's environment, then influence the performance of that plant unit. As a special case, we discuss the mechanisms by which the proxy property wood density has strong correlations to performance but without direct causality. Traits and properties influence multiple aspects of performance, and there can be mutual compensations such that similar performance occurs. This compensation emphasizes that natural selection acts on, and a plant's viability is determined by, its performance, rather than its contributing traits and properties. Continued research on the relationships among traits, and on their effects on multiple aspects of performance, will help us better predict, manage, and select plant material for success under multiple stresses in the future. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  20. Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

    Science.gov (United States)

    Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

    2017-01-01

    Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

  1. Towards embryonic-like scaffolds for skin tissue engineering: identification of effector molecules and construction of scaffolds

    NARCIS (Netherlands)

    Uijtdewilligen, P.J.E.; Versteeg, E.M.M.; Gilissen, C.F.; Reijmersdal, S.V. van; Schoppmeyer, R.; Wismans, R.G.; Daamen, W.F.; Kuppevelt, T.H. van

    2016-01-01

    Autologous skin grafts are the gold standard for the treatment of burn wounds. In a number of cases, treatment with autologous tissue is not possible and skin substitutes are used. The outcome, however, is not optimal and improvements are needed. Inspired by scarless healing in early embryonic

  2. Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

    Directory of Open Access Journals (Sweden)

    Alice C Pong

    Full Text Available Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation.Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25% into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz was used to measure the brain stiffness (G*, shear modulus.Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P < 0.001 for both but there were no significant changes in cranial cross-sectional area (Spearman, P = 0.35, cortical gray matter stiffness (Spearman, P = 0.24 and caudate-putamen (Spearman, P = 0.11 stiffness. No significant changes in the size of brain structures were observed in the controls.This study showed that although brain tissue in the adult hydrocephalic rats was severely compressed, their brain tissue stiffness did not change significantly. These results are in contrast with

  3. Suitability of a PLCL fibrous scaffold for soft tissue engineering applications: A combined biological and mechanical characterisation.

    Science.gov (United States)

    Laurent, Cédric P; Vaquette, Cédryck; Liu, Xing; Schmitt, Jean-François; Rahouadj, Rachid

    2018-04-01

    Poly(lactide-co-ε-caprolactone) (PLCL) has been reported to be a good candidate for tissue engineering because of its good biocompatibility. Particularly, a braided PLCL scaffold (PLL/PCL ratio = 85/15) has been recently designed and partially validated for ligament tissue engineering. In the present study, we assessed the in vivo biocompatibility of acellular and cellularised scaffolds in a rat model. We then determined its in vitro biocompatibility using stem cells issued from both bone marrow and Wharton Jelly. From a biological point of view, the scaffold was shown to be suitable for tissue engineering in all these cases. Secondly, while the initial mechanical properties of this scaffold have been previously reported to be adapted to load-bearing applications, we studied the evolution in time of the mechanical properties of PLCL fibres due to hydrolytic degradation. Results for isolated PLCL fibres were extrapolated to the fibrous scaffold using a previously developed numerical model. It was shown that no accumulation of plastic strain was to be expected for a load-bearing application such as anterior cruciate ligament tissue engineering. However, PLCL fibres exhibited a non-expected brittle behaviour after two months. This may involve a potential risk of premature failure of the scaffold, unless tissue growth compensates this change in mechanical properties. This combined study emphasises the need to characterise the properties of biomaterials in a pluridisciplinary approach, since biological and mechanical characterisations led in this case to different conclusions concerning the suitability of this scaffold for load-bearing applications.

  4. Adipose tissue and adrenal glands: novel pathophysiological mechanisms and clinical applications.

    Science.gov (United States)

    Kargi, Atil Y; Iacobellis, Gianluca

    2014-01-01

    Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unknown whether these changes in adrenal endocrine function are in part responsible for the pathogenesis of obesity and related comorbidities or represent an adaptive response. In turn, adipose tissue hormones or "adipokines" have direct effects on the adrenal glands and interact with adrenal hormones at several levels. Here we review the emerging evidence supporting the existence of "cross talk" between the adrenal gland and adipose tissue, focusing on the relevance and roles of their respective hormones in health and disease states including obesity, metabolic syndrome, and primary disorders of the adrenals.

  5. The mechanism of tissue-restricted antigen gene expression by AIRE.

    Science.gov (United States)

    Zumer, Kristina; Saksela, Kalle; Peterlin, B Matija

    2013-03-15

    The autoimmune regulator is a critical transcription factor for generating central tolerance in the thymus. Recent studies have revealed how the autoimmune regulator targets many otherwise tissue-restricted Ag genes to enable negative selection of autoreactive T cells.

  6. Strain Modulations as a Mechanism to Reduce Stress Relaxation in Laryngeal Tissues

    OpenAIRE

    Hunter, Eric J; Siegmund, Thomas; Chan, Roger W.

    2014-01-01

    Vocal fold tissues in animal and human species undergo deformation processes at several types of loading rates: a slow strain involved in vocal fold posturing (on the order of 1 Hz or so), cyclic and faster posturing often found in speech tasks or vocal embellishment (1–10 Hz), and shear strain associated with vocal fold vibration during phonation (100 Hz and higher). Relevant to these deformation patterns are the viscous properties of laryngeal tissues, which exhibit non-linear stress relaxa...

  7. Adipose Tissue and Adrenal Glands: Novel Pathophysiological Mechanisms and Clinical Applications

    OpenAIRE

    Kargi, Atil Y.; Iacobellis, Gianluca

    2014-01-01

    Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unkn...

  8. ACTIVATION MECHANISMS OF GUT-ASSOCIATED LYMPHOID TISSUE UNDER CHRONIC SOCIAL STRESS CONDITIONS

    Directory of Open Access Journals (Sweden)

    A. M. Kamyshnyi

    2015-01-01

    Full Text Available Stress-induced immune disregulation is a risk factor of autoimmune and inflammatory diseases, but, so far, the mechanisms for this effect are not fully known. Expression levels of specific mRNAs were assessed in gut-associated lymphoid tissue (GALT from Wistar rats subjected to chronic social stress (CSS. Gene expression was evaluated for NR3C1, Adrβ2, as well as IL-1β, IL-17α pro-inflammatory cytokines, and Nlrp, an inflammasome gene. Under the CSS conditions, we have shown altered distribution of RORγt +, FoxP3+, LMP2+, XBP1+ lymphocytes in GALT.The experiments were carried out with female Wistar rats aged 5–6 months. Specific mRNA expression for the target genes was determined by means of real-time PCR performed in a CFX96™ thermocycler («BioRadLaboratories, Inc»,USA. Relative levels of a target gene expression were quantified by the ΔΔCt method, being compared with rat GAPDH reference gene expression. Statistical analysis was performed with available «BioRad СFX Manager 3.1» software. Specific monoclonal rat antibodes were used for detection of immunopositive lymphocytes by means of indirect immunofluorescence technique.CSS development leads to decreased levels of mRNA expression for Nr3c1 and Adrβ2-genes in the GALT cells, being accompanied with unidirectional changes, i.e., increased transcription of pro-inflammatory cytokine mRNAs (IL-1β, IL-17α and Nlrp3-inflammasome genes. These changes are accompanied by decreased FoxP3+/RORγt + cell ratio and predominant Th17 differentiation accompanied by suppressor failure. In addition, CSS development was characterized by unidirectional tendency for increasing total number of LMP2+ lymphocytes and reduced ХВР1+ cell population density in lymphoid structures of rat ileum.The events observed in GALT cell populations under CSS conditions are opposing classical paradigm of the stress response. The CSS-associated effects do not promote immunosuppression, however, are able to cause

  9. Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone

    Energy Technology Data Exchange (ETDEWEB)

    Eneh, C. T. M., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Töyräs, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Jurvelin, J. S., E-mail: jukka.jurvelin@uef.fi [Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211, Finland and Diagnostic Imaging Center, Kuopio University Hospital, P.O. Box 100, Kuopio FI-70029 (Finland); Malo, M. K. H., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Liukkonen, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi [Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211 (Finland); Karjalainen, J. P., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi [Bone Index Finland Ltd., P.O. Box 1188, Kuopio FI-70211 (Finland)

    2016-05-15

    Purpose: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessment by PE ultrasound. Methods: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. Results: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R{sup 2} ≥ 0.493, p < 0.01 and R{sup 2} ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%–16.4%) was about 6% in the cortical thickness assessment in vitro. Conclusions: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated

  10. Interdependency of construction safety hazards from a network perspective: a mechanical installation case.

    Science.gov (United States)

    Liao, Pin-Chao; Guo, Zhonghua; Wang, Tao; Wen, Jing; Tsai, Chung-Han

    2018-02-23

    The assumption that safety hazards in construction projects are independent leads to a weak foundation for risk assessments, and related management strategies may be biased. Therefore, understanding interdependencies of hazards is critical to risk assessment in construction safety. This study proposed a qualitative-quantitative hybrid approach to delineating hazard associations. Based on the hazard network model for an elevator installation, we identified the characteristics of the hazard network and determined critical hazard types based on the hazard associations. The main conclusions are: (a) the hazard network topology is characterized by an extremely sparse hazard association distribution, few